No retraction, correction or concern found when last checked on Oct 18, 2026.

Ecology of aspergillosis: insights into the pathogenic potency of Aspergillus fumigatus and some other Aspergillus species

Caroline Paulussen, John E. Hallsworth, Sergio Álvarez‐Pérez and 5 more

Microbial Biotechnology · 2016 · Review · CC BY

Abstract

Summary Fungi of the genus Aspergillus are widespread in the environment. Some Aspergillus species, most commonly Aspergillus fumigatus , may lead to a variety of allergic reactions and life‐threatening systemic infections in humans. Invasive aspergillosis occurs primarily in patients with severe immunodeficiency, and has dramatically increased in recent years. There are several factors at play that contribute to aspergillosis, including both fungus and host‐related factors such as strain virulence and host pulmonary structure/immune status, respectively. The environmental tenacity of Aspergilllus , its dominance in diverse microbial communities/habitats, and its ability to navigate the ecophysiological and biophysical challenges of host infection are attributable, in large part, to a robust stress‐tolerance biology and exceptional capacity to generate cell‐available energy. Aspects of its stress metabolism, ecology, interactions with diverse animal hosts, clinical presentations and treatment regimens have been well‐studied over the past years. Here, we synthesize these findings in relation to the way in which some Aspergillus species have become successful opportunistic pathogens of human‐ and other animal hosts. We focus on the biophysical capabilities of Aspergillus pathogens, key aspects of their ecophysiology and the flexibility to undergo a sexual cycle or form cryptic species. Additionally, recent advances in diagnosis of the disease are discussed as well as implications in relation to questions that have yet to be resolved.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 18, 2026. Paragraph numbers are ours, so an answer can point at one.

Introduction

1Aspergillus species are widespread in the environment, growing on plants, decaying organic matter, and in soils, air/bioaerosols, in/on animal systems and in freshwater and marine habitats. Aspergilli are also found in indoor environments (surfaces of buildings, air, household appliances, etc.) and in drinking water and dust. The diverse species which make up the Aspergillus genus are able to utilize a wide variety of organic substrates and adapt well to a broad range of environmental conditions (Cray et al., 2013a). They produce asexual conidia that readily become airborne and are highly stress tolerant, and can produce environmentally persistent sexual ascospores (Stevenson et al., 2015a; Wyatt et al., 2015a). Although there are several hundred species in the Aspergillus genus, there are only a few species which have considerable impacts on human or animal health. Infections are typically caused by Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger and Aspergillus terreus, among other species (Baddley et al., 2001; Perfect et al., 2001; Enoch et al., 2006; Gupta et al., in press), with A. fumigatus being responsible for more than 90% of infections, followed in frequency by A. flavus and A. niger (Lass‐Flörl et al., 2005; Balajee et al., 2009a,b). However, the actual contribution of different Aspergillus species in causing aspergillosis varies from country to country and depends on the patient population under study (for some examples, see Table S1 and references therein, supporting information). Furthermore, some infections attributed to the major aspergilli (i.e. A. fumigatus, A. flavus, etc.) might be actually caused by cryptic species1 (see below). Conidia of pathogenic Aspergillus strains that are inhaled by humans or animals are usually eliminated by the innate immune system neutrophils and macrophages in immunocompetent individuals. However, depending on the virulence of the fungal strain, immunological status, and/or the host's pulmonary structure and function, Aspergillus can lead to a variety of allergic reactions and infectious diseases in immunocompromised individuals. This may progress to invasive and lethal infection of the respiratory system (and/or other tissues), often followed by dissemination to other organs, a condition known as invasive aspergillosis. A locally invasive version of the disease, chronic necrotizing pulmonary aspergillosis, is mainly observed in humans with mild immunodeficiency or with a chronic lung disease. Non‐invasive forms of Aspergillus‐induced lung disease include aspergilloma and allergic bronchopulmonary aspergillosis (ABPA) (Kosmidis and Denning, 2015a,b).

2Various factors, including facets of modern living, that contribute to increasing numbers of immunocompromised people include: increases in population longevity; environmental pollution; alcoholism; HIV and other diseases; unhealthy levels of personal hygiene; sedentary lifestyles; obesity; modern medical interventions resulting in high rates of use of prosthetic devices in invasive surgery; chemotherapy and radiotherapy in cancer therapy; and solid organ and bone marrow transplantation requiring the clinical use of immunosuppressive drugs (Maschmeyer et al., 2007). As a result, the number of research studies investigating aspergillosis is increasing; there were 13 456 peer‐reviewed reports on aspergillosis for the period 2006–2015, when compared with 8313 for 1996–2005 and 3231 for 1986–1995, according to the Thomson Reuters Web of Science database (accessed 28 April 2016).

3The success of members of the Aspergillus genus as dominant organisms in diverse habitats is attributable to a combination of interacting factors (Cray et al., 2013a) resulting in a global ubiquity which particularly contributes to the impact of A. fumigatus as a successful opportunistic pathogen. Morphological characteristics, a remarkable stress‐tolerance biology, an ability to penetrate host defences and colonize/damage the host, exceptional ability to generate cell‐available energy, and other aspects of its ecophysiology collectively contribute to its efficacy as a pathogen. The genomes of various Aspergillus species have been sequenced and aspects of their stress metabolism, ecology, and interactions with diverse animal hosts, clinical presentations and treatment regimes are well‐characterized. This said insights from these disparate fields need to be fully synthesized to produce an integrated understanding of Aspergillus behaviour and capabilities in the context of its exceptional levels of virulence. This review will focus on several aspects by which Aspergillus, especially A. fumigatus, has emerged as a ubiquitous opportunistic pathogen which increasingly poses an ominous threat to human health and mortality. More specifically, we explore key aspects of its biophysical capabilities and ecophysiology (Tables 1 and 2), and the flexibility to undergo a sexual cycle or form cryptic species, which contribute to the pathogenic potency of Aspergillus species during the development of infection. Further, we discuss recent advances in diagnosis of aspergillosis, and go on to discuss unresolved scientific questions in the context of further work needed in relation to both fundamental and applied aspects of aspergillosis.

Biophysical capabilities and ecophysiology of pathogenic Aspergillus species

4Collectively, the aspergilli are remarkable fungi. They are not only environmentally ubiquitous; they are also used as the cell factory of choice for many biotechnological applications (Knuf and Nielsen, 2012). Furthermore, there are numerous aspects of Aspergillus cell biology and ecology (including their metabolic dexterity when adapting to nutritional and biophysical challenges) (Tables 1 and 2) which contribute to their status as, arguably, the most potent opportunistic fungal pathogens of mammalian hosts.

5Strains of A. fumigatus, A. flavus, A. niger and other Aspergillus species can inhabit different types of environments.2 These habitats are not only diverse in terms of substrate and implications for fungal lifestyle, but also vary greatly in relation to temperature and water availability regime and the dynamics of other biophysical parameters (Cray et al., 2013a; Rummel et al., 2014; Lievens et al., 2015). Some Aspergillus species, including some strains of A. fumigatus, are xerotolerant, xerophilic and/or capable of surviving repeated desiccation–rehydration cycles (Williams and Hallsworth, 2009; Krijgsheld et al., 2012; Kwon‐Chung and Sugui, 2013; Wyatt et al., 2015b), conditions which can promote sporulation. Indeed, Aspergillus species are renowned for the large‐scale production of hydrophobic and readily airborne spores, including those which colonize building materials (Ko et al., 2002; Afanou et al., 2015; Zhang et al., 2015). Spores of Aspergillus species are among the microbial cells with the greatest longevity; highest tolerances to heat, pressure and chaotropicity; and ability to germinate at the lowest water activity. For example, Aspergillus conidia (most commonly implicated in aspergillosis infection) can survive for 60 years or more (Kwon‐Chung and Sugui, 2013); some structures (ascospores) survive exposure to temperatures of 85°C (Wyatt et al., 2015a); and their conidia have germinated at 0.640 water activity (and may germinate at < 0.600 water activity according to theoretical determinations; A. Stevenson and J. E. Hallsworth, unpublished), which represents the limit for life on Earth (Stevenson et al., 2015a,b).

6Entry into the host system is typically via inhalation of, or contact with, Aspergillus conidia (Table 1). The small size of A. fumigatus conidia (2–3 μm) allow deep penetration of the pulmonary alveoli. Other Aspergillus species, such as A. flavus, produce larger conidia which can be removed more easily by the mucociliary clearance in the upper respiratory tract (Binder and Lass‐Flörl, 2013). Conidia and other spores are invariably desiccated (Bekker et al., 2012; Wyatt et al., 2013), and a rapid recovery from desiccation/short lag phase prior to germination is imperative for pathogenic strains to evade immune responses, and successful infection and invasion of host tissue (Kwon‐Chung and Sugui, 2013). An effective host immune response can take up to 24 h in humans (Cramer et al., 2011). As a result, Aspergillus strains able to penetrate host tissue in a shorter time are more likely to be effective in terms of colonization and subsequent infection of the host. In addition, conidia of A. fumigatus and other species contain melanin which can protect against enzymatic lysis, diverse stresses (see below), and can also inactivate the C3 component of the complement system (which usually plays a key role in the clearance of microorganisms) (Jahn et al., 1997; Abad et al., 2010).

7Lung epithelial cells form a monolayer that can often be the initial point of contact between fungus and host (Osherov, 2012). After adhering to the epithelial cells, conidia are rapidly endocytosed by type II pneumocytes (Zhang et al., 2005). Subsequent to entry into the epithelial cell, the conidium can germinate, a key aspect here is the adherence and subsequent entry of fungal spores to the lung epithelium (Slavin et al., 1988). Aspergillus spores form a diffusible product that is able to inhibit the activity of alveolar macrophages and thereby facilitates this process (Nicholson et al., 1996). Furthermore, proteases are produced by the germinating spores which can damage the epithelial cells (Kauffman, 2003), and finally, the spores invade the vascular endothelium by passing from the abluminal to the luminal side of the pulmonary endothelial cells (Ben‐Ami et al., 2009). This is followed by the emergence of hyphae that can penetrate the abluminal surface of endothelial cells, simultaneously causing cell damage (Table 1). In severely immunocompromised individuals, following angioinvasion, hyphal fragments can disseminate haematogenously leading to invasion of deep organs (Filler and Sheppard, 2006). Some details relating to the mechanical penetration of germ tubes and hyphae into, and mycelial extension within, host tissue have yet to be fully elucidated (Table 1). It is clear, however, that proliferation within the blood vessels adds to the potency of invasive aspergillosis since it leads to tissue necrosis at the foci of infection reducing leucocyte penetration as well as effectiveness of antifungal drugs (Filler and Sheppard, 2006).

8The biophysical challenges encountered both within and without the host, robust stress‐tolerance biology of Aspergillus, ability to compete effectively against other microbes (see below), and other demands of invading host tissue/dealing with immune responses (Tables 1 and 2) all require considerable levels of cell‐available energy. Disparate studies – based on mycelial morphology, stress metabolism, bioinformatic analysis of genomes and ecology – indicate that Aspergillus species indeed have an extraordinary capacity for energy generation (Table 2). Bioinformatic analyses of whole genomes of A. fumigatus, A. flavus, A. nidulans, A. terreus and other species have discovered duplications in a number of genes encoding enzymes involved in metabolic flux at the level of primary metabolism and energy generation, such as those involved in the citric acid cycle and glycolysis (Flipphi et al., 2009). Aspergillus species can also grow via the formation of a floccose mycelium, producing aerial hyphae that are capable of enhanced oxygen absorption and increased rates of respiration; thereby increasing energy generation and tolerance to heat or other stresses (Rahardjo et al., 2005a,b). Studies on A. nidulans, under NaCl‐induced stress, indicate an upregulation of glyceraldehyde‐3‐phosphate dehydrogenase which diverts the utilization of carbon substrate into glycolysis (away from the formation of excessive glycerol) and thereby increases ATP production during stress (Redkar et al., 1998). Aspergillus species are able to utilize a wide range of substrates, highly efficient at acquiring such resources, and can store considerable quantities of nutrients within the cell; all traits which contribute to their energy‐generating capacity and competitive ability (Cray et al., 2013a). Species of Aspergillus are also among the most stress‐tolerant microbes thus far characterized in relation to, for example, low water activity, osmotic stress, resistance to extreme temperatures, longevity, chaotropicity, hydrophobicity and oxidative stress (Table 2) (Hallsworth et al., 2003b; Williams and Hallsworth, 2009; Chin et al., 2010; Krijgsheld et al., 2012; Cray et al., 2013a; Kwon‐Chung and Sugui, 2013; Alves et al., 2015; Stevenson et al., 2015a,b; Wyatt et al., 2015a). Furthermore, aspergilli exhibit the highest tolerances towards ionizing radiation and ultraviolet radiation among other microbes (Dadachova and Casadevall, 2008; Singaravelan et al., 2008).

9Aspergillus species have diverse adaptations and responses to cellular stress, in addition to the reinforcement of energy‐generating capacity. These include the deployment of biophysically diverse compatible solutes and functionally diverse protein‐stabilization proteins; hyperaccumulation of melanin in the cell wall; oxidative stress responses; ability to resist high temperatures; the production of extracellular polymeric substances (EPS) and formation of biofilms; and the ability to compete with other microbes (Tables 1 and 2). Although individual responses are detailed below, many of these are polygenetic traits and, furthermore, multiple responses/adaptations to stress act in concert and/or are connected at the levels of gene expression, metabolic regulation, physiology and biophysics.

10Some Aspergillus strains can synthesize and accumulate glycerol to extraordinarily high concentrations (up to 6–7 M; A. Stevenson and J. E. Hallsworth, unpublished), e.g. for osmotic adjustment (Alves et al., 2015), and mannitol and other polyols which also have unique properties as protectants (e.g. see Hallsworth and Magan, 1995; Rangel et al., 2015a). Aspergilli also produce other amino‐acid compatible solutes which, like compatible solutes, can be effective protectants against chaotrope‐ and hydrophobe‐induced stresses (Bhaganna et al., 2010; Alves et al., 2015); and produce high levels of trehalose and trehalose‐containing oligosaccharides known to protect against desiccation and rehydration events and temperature changes, especially those which occur upon spore germination (Wyatt et al., 2015a,b). Aspergillus species are metabolically wired to deploy each of these substances (or a combination of compatible solutes) according to the biophysical challenges, and this versatility has been associated with germination and hyphal growth at water activities which represent the limit for life (see above) and with extreme temperature tolerances; an ability to function at subzero temperature (due to preferential accumulation of chaotropic compatible solutes such as glycerol: Chin et al., 2010); and ability to stabilize macromolecular systems under conditions which can disorder membranes and other macromolecules (see Ball and Hallsworth, 2015 and references therein)3; and a high level of competitiveness (Cray et al., 2013a). Rehydrating and germinating spores within human or other hosts are subject to biophysically violent changes in hydration, water activity and osmotic stress. Furthermore, cells can undergo temperature changes and may be exposed to chaotropic or hydrophobic substances, such as breakdown products of insect cuticles (Gao et al., 2011; Cray et al., 2015a). In addition, antimicrobials produced by microbes or the animal host commonly‐like many environmental substances ‐ exhibit the same mode‐of‐action (Fang, 1997; James et al., 2003; Hallsworth et al., 2007; Cray et al., 2013b,b, 2015a; Pedrini et al., 2015; da Silva et al., 2015; Yakimov et al., 2015; Bhaganna et al., 2016). Such substances can modify the outcomes of interactions between diverse cells types, although this may reduce or promote infection, depending on a variety of biotic and abiotic factors (Cray et al., 2013a, 2015b, 2016; Suryawanshi et al., 2015). The complexity and versatility of the compatible solutes produced by Aspergillus are akin to those produced by environmentally ubiquitous, tenacious and competitive bacteria such as Pseudomonas putida (Cray et al., 2013a). These compatible solutes play key roles in various types of habitat‐relevant stresses for diverse types of pathogenic aspergilli (Tables 1 and 2; Cray et al., 2013a; Rangel et al., 2015a,b).

11The activities of protein stabilization proteins (e.g. heat shock proteins, cold shock proteins and chaperonins) are essential to enable microbial metabolism under extreme conditions, can support competitive ability, and can even expand microbial growth windows in relation to biophysical parameters (Table 2; Ferrer et al., 2003; Cray et al., 2013a). Such proteins may enhance the flexibility of proteins at low temperature (Fields, 2001; Ferrer et al., 2003), and stabilize protein structure at high temperature or under chaotropicity‐mediated stressors induced by chaotropic solutes, hydrophobic stressors and solvents (Table 2; Hallsworth et al., 2003a; Bhaganna et al., 2010, 2016; Cray et al., 2015a). One study on A. fumigatus identified changes in 64 proteins at temperatures exceeding 37°C, many of these acting as chaperonins (Albrecht et al., 2010). Furthermore, A. fumigatus appears to downregulate genes involved in carbohydrate metabolism at high temperatures in a way that is linked to the upregulation of heat shock proteins, thereby enhancing the speed, efficiency and efficacy of heat shock response (Do et al., 2009). Studies on A. nidulans have identified PalA, a protein, which induces an efficient increase in the production of protein stabilization at extreme pH values (Freitas et al., 2011).

12Melanin has been quantified in A. fumigatus, A. flavus and A. niger at values of 3.4, 1.4 and 2.2 mg ml−1 respectively (Allam and Abd El‐Zaher, 2012; Pal et al., 2014). In Aspergillus spores (as well as their hyphae), this pigment protects against oxidative stress, ultraviolet radiation, ionizing radiation and high temperature by enhancing the rigidity of the cell wall (Dadachova and Casadevall, 2008; Schmaler‐Ripcke et al., 2009; Allam and Abd El‐Zaher, 2012; Upadhyay et al., 2013; Ludwig et al., 2014). It can act as a barrier to host defences (including the generation of free radicals by host macrophages) as well as being able to bind and thereby neutralize antifungal drugs (Nosanchuk and Casadevall, 2006; Upadhyay et al., 2013). Additionally, melanin enables survival of conidia after macrophage phagocytosis, by blocking phagolysosome acidification allowing germination and liberation from the phagocytic cell (Slesiona et al., 2012 ).

13Aspergilli, including some of the species associated with aspergillosis, are highly resistant to mechanistically diverse, cell surface acting inhibitors as well as various heavy metals (Ouedraogo et al., 2011; Jarosławiecka and Piotrowska‐Seget, 2014; Luna et al., 2015). Heavy metals, chaotropic substances, heat and other stresses can induce lipid peroxidation and an oxidative stress response in microbial cells, including high levels of antioxidant enzymes (Hallsworth et al., 2003a; Abrashev et al., 2008; Luna et al., 2015). In A. niger, responses to oxidative stress include increased production of antioxidant enzymes and/or increased concentrations of metabolites with antioxidant activity (Gaetke and Chow, 2003; Luna et al., 2015). Production of enzymes, such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S‐transferase and glutathione reductase is increased by up to 25% in response to copper‐induced oxidative stress in A. niger (see also Table 2; Luna et al., 2015). Such enzymes detoxify superoxide anions and hydrogen peroxide, although in each case the mechanism may differ (Table 2 and references therein).

14By comparison with other disease‐causing species, A. fumigatus is more thermotolerant and ascospores can survive temperatures of 85°C (Wyatt et al., 2015a). Growth is feasible at 55°C and is optimal at 37°C (Beffa et al., 1998; Ryckeboer et al., 2003). Two genes, thtA and cgrA, are believed to be involved in the thermotolerance of A. fumigatus, but they do not seem to contribute to pathogenicity (Chang et al., 2004; Bhabhra and Askew, 2005). Yet, no conserved set of genes has been firmly linked to thermotolerance or fungal growth at different temperatures (Nierman et al., 2005). Do et al. (2009) suggesting that thermotolerance might be due to the efficient regulation of metabolic genes by heat shock proteins.

15Further, it has become clear that Aspergillus species can produce biofilms on abiotic or biotic surfaces, an ability which impacts clinical medicine (reviewed in Ramage et al., 2011). Previous studies revealed that biofilm formation by Aspergillus is induced by a complex interplay of different fungal constituents, such as cell wall components, secondary metabolites and drug transporters (Fanning and Mitchell, 2012). Biofilm formation and production of EPS is an important determinant in the development of aspergillosis (Table 1) as EPS and biofilms can also protect against stresses induced by antimicrobials and microbial competitors (Cray et al., 2013a and references therein).

16The main classes of antifungas used for treatment of aspergillosis are: inhibitors of the ergosterol biosynthesis pathways (i.e. triazoles and allylamines); compounds which bind to sterols thereby damaging cellular membranes i.e. (polyenes); and compounds which act as inhibitors of synthesis of 1,3‐β‐d‐glucan, an important cell‐wall component (i.e. echinocandins) (Ellis, 2002; Greer, 2003; Chen et al., 2011; Vandeputte et al., 2012). Susceptibility/resistance of Aspergillus strains to antifungals can vary; e.g. some may possess mutations in specific genes, such as the cyp51 gene encoding a 14‐α‐demethylase involved in the ergosterol biosynthesis pathway (Vermeulen et al., 2015), heat shock proteins, melanin (see above), efflux pumps and/or biofilm formation (Seidler et al., 2008; Kaur and Singh, 2014; Oliveiria and Caramalho, 2014). EPS can prevent diffusion of echinocadins into the biofilm, thereby protecting the fungus (Seidler et al., 2008). Aspergillus strains occupy diverse habitats, whether located within a human host, soils or other environments (Delhaes et al., 2012; Cray et al., 2013a). The genomes of Aspergillus species typically have large numbers of clusters of secondary metabolite biosynthetic genes and are capable of producing diverse types of antimicrobial substances (Cray et al., 2013a), contributing to their ability to thrive and dominate in diverse microbial communities. For instance, Flewelling et al. (2015) found that A. fumigatus isolate AF3‐093A produces antimicrobials, such as flavipin, chaetoglobosin A and chaetoglobosin B, which are potent inhibitors of bacteria including Staphylococcus aureus, methicillin‐resistant S. aureus and Mycobacterium tuberculosis H37Ra. Pseudomonas aeruginosa, which commonly infects the lungs of cystic fibrosis patients (Smith et al., 2015), releases metabolites that are known to inhibit fungal growth (Mowat et al., 2010). This bacterium – notorious for its ecologically aggressive character as a microbial weed (Cray et al., 2013a) – can, for instance, inhibit biofilm formation by A. fumigatus. It does not appear to break down extant A. fumigatus biofilms (Mowat et al., 2010). Furthermore, P. aeruginosa has been found to inhibit formation of mycelium, upon germination of A. fumigatus conidia, by approximately 85% relative to mycelial biomass from control A. fumigatus conidia that were not exposed to bacterial cells (Mowat et al., 2010). Nevertheless, A. fumigatus can also be an effective competitor of P. aeruginosa, and strains of this fungus have frequently been isolated from the lungs of cystic fibrosis patients (Mowat et al., 2010); outcomes of such interspecies interactions are determined by a complex range of interacting variables (Cray et al., 2013a; in press). Metabolic versatility of A. flavus, A. nidulans and other Aspergillus species has also been associated with ecological vigour in nutritionally diverse environments, including host tissues (Cray et al., 2013a; Mehl and Cotty, 2013). The ability of A. flavus to produce a broad spectrum of degrading enzymes and to infect a wide variety of plant or animal hosts, and to use non‐living substrates suggests it is an opportunistic pathogen capable of subsisting on a diverse range of nutritional sources (Mellon et al., 2007; Mehl and Cotty, 2011). Furthermore, drug‐resistant strains of A. fumigatus do not appear to suffer from any reduction in ecological fitness (Valsecchi et al., 2015).

Clinical manifestations and diagnosis of aspergillosis

17Although the main portal‐of‐entry and site‐of‐infection for Aspergillus in human hosts is the respiratory tract, other foci for penetration and infection have also been described (Lortholary et al., 1995; Denning, 1996). The clinical manifestations of aspergillosis vary and can be divided into three main categories, according to the location and extent of colonization and invasion (both of which are influenced by the fungal virulence and immune response of the host); these are (i) allergic reactions, (ii) chronic pulmonary aspergillosis and (iii) invasive aspergillosis. Aspergillus species can also colonize the host without causing a systemic infection – at sites such as the eyes, ears and skin – although reports of non‐invasive Aspergillus within such body locations are considerably less common than those of aspergillosis (Richardson and Hope, 2003). Allergic diseases caused by Aspergillus can be associated with asthma, sinusitis and alveolitis and occur following repeated exposure to conidia and/or Aspergillus antigens (Denning et al., 2014). In such cases, there is usually no mycelial colonization, so removal of the patient from the environmental source results in clinical improvement (Latgé, 1999). ABPA is considered as an extreme form of A. fumigatus‐induced asthma. In this case, the fungus grows saprophytically in the bronchial lumen, resulting in bronchial inflammation (Steinbach, 2008). The conidia trigger an IgE‐mediated allergic inflammatory response, leading to bronchial obstruction (Agarwal et al., 2015). Symptoms are recurrent fever, cough, wheezing, pulmonary infiltrates and fibrosis (Barnes and Marr, 2006). ABPA is observed in a small but numerically significant fraction of patients with asthma or cystic fibrosis (1–2% or 8–9% of the total, respectively) (Maturu and Agarwal, 2015).

18Chronic pulmonary aspergillosis is a progressive cavitary lung disease, which can be accompanied by development of dense balls of fungal mycelium (that are known as aspergilloma) (Schweer et al., 2014). These balls are a non‐invasive, saprophytic form of Aspergillus that colonize pre‐existing pulmonary cavities, which were formed during tuberculosis or other pulmonary disease (Steinbach, 2008). People with aspergilloma may be asymptomatic, although many suffer from a persistent and productive cough, haemoptysis and weight loss (Babu and Mitchell, 2015). Regarding the second category, there are different forms of chronic pulmonary aspergillosis, depending on the development of infection and the host's immune status. Most common are chronic necrotizing pulmonary aspergillosis and chronic cavitary pulmonary aspergillosis. Although the first one causes the progressive destruction of lung tissue, chronic cavitary pulmonary aspergillosis can cause multiple cavities, with or without aspergilloma, accompanied by pulmonary and systemic symptoms (Ohba et al., 2012).

19Finally, a third category of aspergillosis is invasive aspergillosis, representing the most life‐threatening opportunistic fungal infection in patients with reduced immunity. Invasive pulmonary aspergillosis is the most common form of invasive aspergillosis, implying fungal invasion in the lung tissue. Patients at risk are predominantly haematopoietic stem‐cell transplant recipients and patients with haematological malignancies undergoing intensive chemotherapy; however, cases involving non‐neutropenic patients have also been reported (Kosmidis and Denning, 2015a,b). Acute invasive rhinosinusitis is an underdiagnosed form of invasive aspergillosis which most commonly involves the maxillary sinus, followed by the ethmoid, sphenoid and frontal sinuses; this type of infection is aggressive and often fatal (Drakos et al., 1993; Middlebrooks et al., 2015). Finally, disseminated disease (fungaemia) involves systemic invasion of the brain and other organs, such as kidneys, heart, skin and eyes (Latgé, 1999; Singh and Husain, 2013).

20Diagnosis of the different forms of aspergillosis presents a major challenge in medicine for several reasons, including the non‐specific nature of their clinical presentation, the lack of a sensitive and accurate diagnostic assay to ensure an early diagnosis, and the fact that pathogenic aspergilli can only be rarely isolated from infected persons (Thornton, 2010; Lackner and Lass‐Flörl, 2013). The most important diagnostic criteria for invasive aspergillosis are as follows: clinical and radiological evidence of lower respiratory tract infection; biological criteria including direct microscopic evaluation, isolation, culture, and definitive identification of Aspergillus from a clinical specimen, or evidence from immunological, serological and/or molecular tests; host‐related characteristics, such as neutropenia or persistent fever in high‐risk patients; and histopathological evidence of infection (De Pauw et al., 2008; Paulussen et al., 2014). An important advantage of culture‐based assays is that isolates are obtained which can be used in epidemiological studies and for the development of new antifungals that are likely to be effective within clinical treatment regimes. However, an Aspergillus strain isolated from an infected patient may or may not be the primary causal agent of the aspergillosis infection as multiple fungal strains, some highly pathogenic and others not, may be present (Álvarez‐Pérez et al., 2009; Arvanitis and Mylonakis, 2015; Escribano et al., 2015).

21A variety of immunological tests are available that can be used to diagnose the disease (Arvanitis and Mylonakis, 2015). Assays based on antibody detection have been successful to diagnose allergic aspergillosis and aspergilloma, while assays for fungal antigen detection showed great potential in diagnosing invasive aspergillosis (Richardson and Hope, 2003; Lackner and Lass‐Flörl, 2013). Further, PCR‐based assays have been developed that can improve early diagnosis of aspergillosis. Advantages of such molecular assays include a high sensitivity, ability to establish diagnosis at the species level and capacity to detect genes that confer antifungal resistance (Segal, 2009). In addition, PCR is fast, inexpensive and can be applied to diverse types of sample, such as blood, sputum and tissue. However, PCR‐based methods have not yet found their place in clinical practice mainly due to lack of standardization (Arvanitis and Mylonakis, 2015). When using PCR, special care must be taken to avoid false‐positive results, e.g. caused by conidia commonly present in the air and airways of non‐infected patients (Bart‐Delabesse et al., 1997). The European Aspergillus PCR Initiative has made significant progress in developing a standard real‐time quantitative PCR protocol, but its clinical utility has to be established in formal and extensive clinical trials (Gomez, 2014). PCR should, therefore, still be used in conjunction with other methods, such as serological assays or radiological methods, to diagnose aspergillosis (Morrissey et al., 2013).

Sexual cycle and cryptic species: implications for virulence

22Recent advances in the fields of genomics, cell biology and population genetics have reshaped our view of how fungal pathogens reproduce and might be evolving. Some species, traditionally regarded as asexual, mitotic and largely clonal, are now being examined in the context of their (cryptic) sexuality (Heitman et al., 2014; Varga et al., 2014). In this regard, while most known Aspergillus species – approximately two‐thirds of the total number have not yet been demonstrated to possess a functioning sexual cycle (Dyer and O'Gorman, 2012), there has been a remarkable discovery of sexual stages (also known as teleomorphs) for aspergilli that were hitherto assumed to be asexual, such as A. fumigatus (O'Gorman et al., 2009), A. flavus (Horn et al., 2009b) and Aspergillus parasiticus (Horn et al., 2009b). Notably, these three species were found to be heterothallic (i.e. with obligate outcrossing), which contrasts with the homothallism (i.e. self‐fertilization) of most sexual aspergilli (Lee et al., 2010; Dyer and O'Gorman, 2012). In addition, it is known that some Aspergillus species can undergo a parasexual cycle that enables genetic recombination during mitosis (Pontecorvo et al., 1953; Lee et al., 2010; Varga et al., 2014).

23The discovery of a sexual cycle for Aspergillus species has not been casual, but is the result of years of intense research work and accumulating evidence from different fields, including ‘‐omics’ sciences, population genetics and the analysis of the phylogenetic relationships with sexually reproducing species (Dyer and Paoletti, 2005; Paoletti et al., 2005; Álvarez‐Pérez et al., 2010a,b; Dyer and O'Gorman, 2012; Heitman et al., 2014). Importantly, although the discovery of a functional set of genes necessary for sexual developmental processes (also known as mating type [MAT] genes) in the genome sequence of some species is usually given a predominant role in this search for the hidden sexuality of the aspergilli, the diagnostic value of basic mycological techniques, such as paired mating and microscopic observation of the development of mature sexual structures, should not be overlooked.

24But, why might an opportunistic pathogen like A. fumigatus need to maintain a fully operative sexual cycle when asexual conidia are so abundantly produced and effective as infecting propagules? And how frequently do pathogenic aspergilli reproduce sexually in nature? Unfortunately, the answers to these questions remain unknown and, furthermore, might not be so easy to obtain. A prevailing hypothesis which may lead to an explanation for the maintenance of a sexual cycle in some aspergilli is that sexual reproduction might provide important benefits, such as the possible generation of new combinations of beneficial traits, the purging of deleterious mutations and the formation of thick‐walled fruiting bodies that are resistant to harsh environmental conditions (Lee et al., 2010; Dyer and O'Gorman, 2012). Nevertheless, sexual reproduction has, in most cases, a 50% cost (i.e. the sexually reproducing organism is only able to pass on 50% of its genes to a progeny); requires considerable investment in time and energy; and can break apart favourable combinations of alleles, potentially reducing fitness (Lee et al., 2010). Despite the inherent advantages of sexual reproduction for living systems, it has been suggested that successful fungal pathogens might be undergoing a slow decline in sexual fertility which, eventually, could lead to permanent asexuality (Dyer and Paoletti, 2005). Upon discovery of the A. fumigatus teleomorph, it has been suggested that the sexual fertility of A. fumigatus might be limited to some isolates of certain geographically restricted populations (O'Gorman et al., 2009). However, sexual fertility has now been demonstrated for many isolates from diverse global locations, and some of these even displayed high mating efficiency (Sugui et al., 2011; Camps et al., 2012). An apparent decline in sexual fertility has also been suggested for some emerging agents of aspergillosis, such as Aspergillus udagawae and Aspergillus lentulus, which frequently fail to produce cleistothecia in paired matings or produce ascospores that do not germinate (Sugui et al., 2010; Swilaiman et al., 2013), but the existence of rare supermater (i.e. highly fertile) individuals within these species cannot be yet excluded.

25Another intriguing research question is the possible effects of sexual reproduction on fungal virulence. The main cause of concern for the medical community is the possible emergence of recombinant strains with increased virulence and/or antifungal resistance (Álvarez‐Pérez et al., 2010a,b; Heitman et al., 2014). In this respect, Camps et al. (2012) demonstrated that azole‐resistant isolates of A. fumigatus with the TR34/L98H mutation (L98H substitution plus a 34‐bp tandem repeat in the promoter region of the cyp51A gene) can successfully mate with azole‐susceptible A. fumigatus isolates of different genetic backgrounds and give rise to a recombinant progeny displaying distinct phenotypes. Although a detailed study of the genetic structure of A. fumigatus in the Netherlands (where multitriazole resistance first emerged) concluded that the TR34/L98H allele seems to be confined to a single, predominantly non‐recombining population of the fungus (Klaassen et al., 2012), sexual reproduction might have played a role in the genetic diversification of azole‐resistant A. fumigatus strains (Camps et al., 2012).

26Mating type related differences in virulence have been explored in some clinically important aspergilli, including A. fumigatus. For example, Álvarez‐Pérez et al. (2010a,b) found an almost fourfold higher frequency of the MAT1‐1 than the MAT1‐2 mating type among A. fumigatus isolates obtained from cases of invasive aspergillosis, while both mating types were represented in a similar proportion among isolates of non‐invasive origin. Furthermore, in the same study the authors found a significant association between the MAT1‐1 mating type and increased elastase activity, which is considered to be a relevant virulence factor (or virulence determinant)4 of A. fumigatus (Blanco et al., 2002; Álvarez‐Pérez et al., 2010a,b). The possible association between the MAT1‐1 mating type and A. fumigatus virulence was confirmed in an insect model system (the wax moth Galleria mellonella) injected with strains of clinical and environmental origin (Cheema and Christians, 2011). However, as A. fumigatus virulence is multifactorial, assessment of the specific contribution of the MAT locus in virulence is not possible unless the strains used in the experiments are congenic except for the MAT locus. Via the latter approach, Losada et al. (2015) have recently demonstrated in three different animal models (mice with chronic granulomatous disease, BALB/c mice immunosuppressed with hydrocortisone acetate and G. mellonella larvae) challenged with an isogenic pair of A. fumigatus strains of opposite mating types, no difference in virulence between them or in the manner by which these caused the disease. Nevertheless, research experience with other fungal pathogens has shown that differences in virulence between mating types can depend on the genetic background of the strains (see, e.g. Nielsen et al., 2005), making necessary the use of different pairs of isogenic strains to reach reliable conclusions. Further research on the role of the MAT locus on A. fumigatus virulence is therefore required.

27The classification of aspergilli has traditionally relied on microscopic and visual determinations of cellular structures and colony morphology as well as key physiological activities (Houbraken et al., 2014). However, the use of multilocus phylogenies and comparative genomics has enabled a refinement of Aspergillus taxonomy (Houbraken et al., 2014; Samson et al., 2014). For example, genetic characterizations of isolates hitherto regarded as atypical strains of A. fumigatus have resulted in their reclassifications as novel species. These distinct species, that nevertheless share a common morphology, commonly referred to as ‘cryptic’ or ‘A. fumigatus‐like’, include A. lentulus (Balajee et al., 2005) and Aspergillus felis (Barrs et al., 2013). Cryptic species have also been recognized for A. niger (e.g. Aspergillus awamori; Perrone et al., 2011), A. parasiticus (e.g. Aspergillus novoparasiticus; Gonçalves et al., 2012), A. terreus (e.g. Aspergillus alabamensis; Balajee et al., 2009a) and Aspergillus ustus (e.g. Aspergillus calidoustus; Varga et al., 2008). So far, Aspergillus species identification based on molecular biology approaches has typically been based on sequencing of the nuclear ribosomal internal transcribed spacer region (Schoch et al., 2012). However, different studies have shown that sequence analysis of some protein‐encoding loci, including the beta‐tubulin (benA) and calmodulin (calM) genes, provides a superior discriminative resolution (Samson et al., 2007, 2014; Houbraken et al., 2014). Sequence analysis of the MAT loci has also proven useful according to several studies (e.g. Barrs et al., 2013; Álvarez‐Pérez et al., 2014; Sugui et al., 2014). This said, a polyphasic approach which includes morphological, physiological, molecular, biochemical and ecological data is likely to be the most informative for resolving taxonomic differences (Samson et al., 2007, 2014).

28The prevalence of the cryptic species among pathogenic aspergilli is still unclear, but they could account for > 10% of the total clinical isolates (Balajee et al., 2009b; Alastruey‐Izquierdo et al., 2012, 2013; Negri et al., 2014). Nevertheless, reports on their occurrence vary, which could be due to differences in study design (e.g. selection of patient populations) and/or variations in geographic distribution of some species (Alastruey‐Izquierdo et al., 2012). Factors, such as increasing awareness among medical practitioners of the importance of the cryptic species (which in turn may lead to a greater research effort), ongoing development of improved techniques for species‐based identification, may also contribute to discrepancies between frequency reports for cryptic species. Some of the cryptic Aspergillus species show a decreased susceptibility to a large number of antifungal drugs when compared with other aspergilli (Alastruey‐Izquierdo et al., 2012, 2013; Howard, 2014; Nedel and Pasqualotto, 2014). Therefore, accurate identification of clinical isolates is critical for effective, targeted antifungal treatment (Alastruey‐Izquierdo et al., 2012, 2013). Some cryptic species do not have predictable susceptibility patterns and therefore, in‐vitro susceptibility testing still remains an invaluable tool to aid directed antifungal therapy (Howard, 2014).

29In addition to the increased antifungal resistance generally attributed to the cryptic aspergilli, some studies have reported significant differences in pathogenicity between sibling species. For example, Coelho et al. (2011) reported that infection by a fungus first identified as Aspergillus viridinutans in an immunocompromised patient led to a distinctive form of invasive aspergillosis characterized by increased chronicity and a propensity to spread across anatomical planes, which contrasts with the rapidly progressive disease which is characterized by a predilection for angioinvasion and haematogenous dissemination typically caused by A. fumigatus. Subsequent polyphasic taxonomic re‐examination of one of the isolates from that case (isolate CM 5623) suggested that it belonged to a novel species designated as A. felis, which also causes invasive aspergillosis in dogs and cats (Barrs et al., 2013). Finally, a recently refined phylogeny placed isolate CM 5623 into a separate clade and justified the proposal of yet another new cryptic representative (designated as Aspergillus parafelis) within the broadly circumscribed species A. viridinutans (Sugui et al., 2014). Notably, A. parafelis and the closely related species, Aspergillus pseudofelis and Aspergillus pseudoviridinutans, which were also proposed as novel taxa in the same study, displayed reduced susceptibility to amphotericin B, itraconazole and voriconazole, and increased virulence in different animal models with respect to the type strain of A. viridinutans (Sugui et al., 2014). Two implications/consequences of this are: (i) the taxonomy of the genus Aspergillus is far from being settled; and (ii) clinicians require some basic knowledge on fungal taxonomy and the cryptic species concept, as these can have consequences for disease management. Furthermore, some cryptic species such as A. parafelis and A. pseudofelis have shown successful mating under laboratory conditions with related species, including A. fumigatus (Sugui et al., 2014). In any case, despite these few exceptions of promiscuous mating, interspecies crossings in the section Fumigati of genus Aspergillus are generally infertile, which suggests that most phylogenetically distinct species are also sexually incompatible (Sugui et al., 2014).

Aspergillus‐related factors implicated in virulence

30Several traits have been postulated to explain the opportunistic behaviour of Aspergillus, including fungus‐related factors as well as host‐related factors (see below) (Fig. 1). A. fumigatus displays a unique combination of traits that can support its virulence (Dagenais and Keller, 2009). For example, the conidial surface is composed of hydrophobic RodA protein covalently bound to the cell wall, collectively known as the rodlet layer. One important function of this layer is conidial dispersion and soil fixation, but it also masks recognition of conidia by the immune system and hence prevents immune response (Aimanianda et al., 2009). Further, recent studies have shown that galactosaminogalactan (GAG), a component of the Aspergillus cell wall that is expressed during conidial germination and hyphal growth, has possible anti‐inflammatory effects. GAG induces the anti‐inflammatory cytokine interleukin‐1 receptor antagonist, making individuals more susceptible to aspergillosis (Gresnigt et al., 2014). Mycotoxins and fungal enzymes are likely to play an important role in the interaction between Aspergillus species and their host. For A. fumigatus, several conidial toxins have been described, in addition to a number of toxins released by hyphae (Mitchell et al., 1997; Kamei and Watanabe, 2005). Five mycotoxins have been identified in A. fumigatus, including gliotoxin, fumagillin, helvolic acid, fumitremorgin A and Asp‐hemolysin. The most studied is gliotoxin, a metabolite in the epipolthio‐dioxopiperazine family that modulates the immune response. Gliotoxin can affect circulating neutrophils, suppresses reactive oxygen species (ROS) production and inhibits phagocytosis of conidia (Scharf et al., 2012). Important mycotoxins produced by other Aspergillus spp. include aflatoxin, ochratoxin, patulin and citrinin, which can be carcinogenic and/or have a major role in food poisoning (Sweeney and Dobson, 1998). Proteolytic enzymes secreted by Aspergillus species, such as serine, metallo and aspartic proteases, are also known to aid virulence (Bergmann et al., 2009). Aspergillus species secrete a variety of proteases, many of which enable the fungus to saprotrophically utilize animal and vegetable matter. Recently, it has been found that many proteases, e.g. those with elastinolytic activity, also function as virulence factors by degrading the structural barriers of the host and thereby facilitating the invasion of host tissues. Elastin constitutes nearly 30% of lung tissue and elastinolytic activity has been implicated in the pathogenesis of Aspergillus (Kothary et al., 1984; Blanco et al., 2002; Binder and Lass‐Flörl, 2013). Further, trace metal ions, such as iron and zinc, have been shown to contribute to virulence. Iron, for example, is a necessary component of many biosynthetic pathways in fungi and is therefore also essential for pathogenesis. Because free iron is scarce in the human body, A. fumigatus produces siderophores (low‐molecular mass iron‐specific chelators) to transport or store ferric ions (Haas, 2012). Zinc is also essential for a wide variety of biochemical processes in fungi, for the adequate regulation of gene expression and thus for cellular growth and development. A clear relationship has been shown between zinc homeostasis and virulence of A. fumigatus, which requires the zinc transporters ZrfA, ZrfB and ZrfC for growth within a host (Moreno et al., 2007; Amich and Calera, 2014). The wide spectrum of disease states greatly complicates the study of putative virulence factors. Moreover, some virulence factors are active mainly in fungi infecting compromised patients such as those with neutropenia or those receiving, corticosteroid therapy (Hogan et al., 1996). It can be expected that additional virulence factors and drug targets can be identified using novel approaches based on whole‐genome sequencing and investigating large collections of fungal strains. In this regard, several studies involving genomic sequencing and subsequent mutant screening have already pointed towards additional gene products that may play key roles in Aspergillus pathogenicity (Valiante et al., 2015).

Host‐related factors implicated in virulence

31In addition to fungus‐related factors, host‐related characteristics may be equally, or even more, important in development of aspergillosis. Immunity against Aspergillus depends on host responses of the innate and adaptive immune system. As described above, A. fumigatus is an opportunistic pathogen which is rarely pathogenic in immunocompetent hosts; the immune system kills fungal intruders thereby preventing infection. As such, immunosuppressive therapies and conditions that compromise the immune system trigger the development of aspergillosis (Latgé, 2001). Innate immunity consists of three major lines of defence including anatomical barriers, humoral factors and phagocytic cells (Latgé, 1999). Upon inhalation of Aspergillus conidia, the majority of conidia are excluded from the lungs through mucociliary clearance. Lung surfactant enhances agglutination, phagocytosis and killing of conidia by alveolar macrophages and neutrophils. In cystic fibrosis patients, many of these mechanisms are dysfunctional, making these patients highly vulnerable for fungal colonization (Noni et al., 2015). Although alveolar macrophages form the first line of defence against inhaled conidia, little is known about their recognition and activation mechanisms. Lectin‐like interactions might be responsible for adherence and uptake of conidia, and also 1,3‐b‐D‐glucan seems to play a role in the conidial binding (Latgé, 2001). The antimicrobial systems via which host cells kill intracellular conidia have not yet been fully characterized.

32After fungal germination, polymorphonuclear neutrophils provide the dominant host defence, rendering neutropenic patients at an elevated risk for developing aspergillosis (Kosmidis and Denning, 2015a,b). In the phagocytes, NADPH‐oxidase catalyses the conversion of oxygen to superoxide anion and the generation of ROS displaying antimicrobial activity (Segal, 2009). The ability of neutrophils to attack and kill Aspergillus depends on pathogen‐recognition receptors, such as toll‐like receptors (TLR2 and TLR4), dectin‐1, surfactant proteins (A and D) and lectin (Singh and Paterson, 2005; Segal, 2009). Natural killer cells are also important effector cells which play a role in host response to invasive aspergillosis, and are recruited to the lungs as an early defence mechanism (Morrison et al., 2003). Natural killer cells are known to mediate immunity against intracellular pathogens (Morrison et al., 2003), but their exact role in the immune response against fungi has yet to be studied in detail. Dendritic cells can transport hyphae and conidia of A. fumigatus from the airways to the draining lymph nodes and thus initiate disparate responses of T‐helper cells to the fungus (Bozza et al., 2002). Following activation of pathogen‐recognition receptors, molecules are released to trigger other players in the immune response to microbial invaders, such as T‐cells, bridging key responders of the innate and adaptive immunity. When the immune system is eventually unable to stop or control hyphal growth, hyphae invade and destroy the surrounding tissue to obtain the necessary nutrients, and, depending on the state of immunosuppression, may cause a disseminated disease (Dagenais and Keller, 2009). Additional research is needed to further unravel the complex interplay between innate and adaptive immunity as key players of aspergillosis, related to different Aspergillus strains exhibiting different pathogenicity.

General conclusions and unanswered questions

33Early diagnosis of Aspergillus infection has been shown to significantly increase the survival rate of the patient (Nucci et al., 2013). However, so far, universally validated diagnostic assays that enable rapid and accurate detection of this potentially deadly fungus have not yet found their way in routine diagnosis of aspergillosis. Furthermore, as aspergillosis can be caused by multiple Aspergillus species, including an increasing number of cryptic species, extreme caution should be taken to avoid false negatives (e.g. due to possible unknown differences in the molecular targets of diagnostic tests). Therefore, work is needed on the development of standardized, rapid and highly sensitive diagnostic assays for use in clinical settings without resorting to time‐consuming culturing, e.g. by targeting a conserved gene involved in the pathogenicity of the fungus (Lievens et al., 2008). Furthermore, attention should also be given to the occurrence of a sexual or parasexual cycle in Aspergillus, as it has been suggested that recombination may give rise to new genotypes with increased virulence (Álvarez‐Pérez et al., 2010a,b; Camps et al., 2012).

34Mortality linked to invasive aspergillosis remains very high despite the availability of new therapeutic strategies. Azole resistance is an emerging problem in A. fumigatus and other Aspergillus species, and is associated with an increased probability of treatment failure (Denning and Perlin, 2011; Seyedmousavi et al., 2014). In addition, particular attention should be given to the increasing occurrence of cryptic species as these are typically linked to an increased antifungal resistance and different pathogenicity (Alastruey‐Izquierdo et al., 2012, 2013; Howard, 2014; Nedel and Pasqualotto, 2014). Furthermore, there is a strong appreciation that stress responses and biofilm formation are involved in drug adaptation, which can ultimately lead to development of higher‐level resistance and diminished clinical response (Kaur and Singh, 2014; Perlin et al., 2015). In this context, a better understanding of the global magnitude of the azole resistance problem and new therapeutic strategies (e.g. novel dosing mechanisms or introduction of new drugs with novel mechanisms of action, such as biofilm inhibitors) are urgently needed (Denning and Perlin, 2011; Kaur and Singh, 2014).

35Aspergillus infections pose considerable challenges due to the complexity of the disease, involving pathogen‐, environment‐ and host‐related factors, and the limitations of current diagnostic tools and therapeutic options. Gaining more insight about both the pathogen and host traits as well as the environmental factors, phenotypic traits and evolutionary trajectory which enable Aspergillus species to cause disease is crucial to fully understand the interaction between the pathogen and the host, as well as to open new therapeutic perspectives. However, despite intensive research, the inner workings of some of the mechanisms and strategies employed by Aspergillus remain enigmatic. For instance, how is it that out of all the fungi, it is Aspergillus which is uniquely equipped to evade host defences in such a precise and consistent manner? Why is it that some Aspergillus species that are closely related to and share important features with A. fumigatus, such as resistance to itraconazole or temperature extremes – e.g. Aspergillus fischeri and Aspergillus oerlinghausenensis (Houbraken et al., 2016) – do not typically behave as opportunistic pathogens. Is it because A. fumigatus is more widely spread in the environment, can enter the human host and evade the immune system more successfully, grows well at 37°C or is it better adapted to microenvironments such as the human body that are often characterized by low nutrient and oxygen availability (Tables 1 and 2; Hall and Denning, 1994; Hillmann et al., 2015a,b; Kroll et al., in press)? A. fumigatus, in particular, and aspergilli in general are very highly evolved and successful soil saprophytes and the competition they face in the soil environment has provided some species or strains most probably with the ability to colonize and cause disease in a compromised human or animal host upon entering the lungs (Tekaia and Latgé, 2005). Furthermore, the question arises: what impact these pathogens have had on the structure of the lung and immune system during human and animal evolution? And how can xerotolerant Aspergillus species and, moreover, extreme xerophiles, such as A. niger and A. penicillioides, be so successful as pathogens in the high‐water activity habitat of the human host? Can the energy generation capability of Aspergillus play a part in enhancing resistance or tolerance to viral infection and thereby enhance vigour, competitive ability and virulence? It seems paradoxical that a genus which is so ubiquitous in various ecosystems and habitats of the Earth's biosphere is equally competent at invading and proliferating in closed systems, including those represented by food fermentations, microbially contaminated spacecraft (see Rummel et al., 2014 and references therein) and an animal or human host. To conclude, only with an integrated research approach bringing together expertise from different disciplines, including mycology, medicine, epidemiology, biopharmaceutical research, ecology, taxonomy and systematics, molecular biology and bioinformatics we will be able to better understand the behaviour and management of this intriguing pathogen.

References 305

1.
Abad, A., Fernandez‐Molina, J.V., Bikandi, J., Ramirez, A., Margareto, J., Sendino, J., et al (2010 ) What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis. Rev Iberoam Micol 27: 155–182.
Not in our library10.1016/j.riam.2010.10.003
2.
Abadio, A.K.R., Kioshima, E.S., Teixeira, M.M., Martins, N.F., Maigret, B., and Felipe, M.S.S. (2011 ) Comparative genomics allowed the identification of drug targets against human fungal pathogens. BMC Genom 12: 75–84.
Not in our library10.1186/1471-2164-12-75
3.
Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing · 2015
Corrected
4.
Abrashev, R., Dolashka, P., Christova, R., Stefanova, L., and Angelova, M. (2005 ) Role of antioxidant enzymes in survival of conidiospores of Aspergillus niger 26 under conditions of temperature stress. J Appl Microbiol 99: 902–909.
Not in our library10.1111/j.1365-2672.2005.02669.x
5.
Abrashev, R., Pashova, S.B., Stefanova, L.N., Vassilev, S.V., Dolashka, P.A.A., and Angelova, M.B. (2008 ) Heat‐shock‐induced oxidative stress and antioxidant response in Aspergillus niger 26. Can J Microbiol 54: 977–983.
Not in our library10.1139/w08-091
6.
Afanou, K.A., Straumfors, A., Skogstad, A., Skaar, I., Hjeljord, L., Skare, O., et al (2015 ) Profile and morphology of fungal aerosols characterized by Field Emission Scanning Electron Microscopy (FESEM). Aerosol Sci Technol 49: 423–435.
Not in our library10.1080/02786826.2015.1040486
7.
Agarwal, R., Aggarwal, A.N., Sehgal, I.S., Dhooria, S., Behera, D., and Chakrabarti, A. (2015 ) Utility of IgE (total and Aspergillus fumigatus specific) in monitoring for response and exacerbations in allergic bronchopulmonary aspergillosis. Mycoses 59: 1–6.
Not in our library10.1111/myc.12423
8.
Aimanianda, V., Bayry, J., Bozza, S., Kniemeyer, O., Perruccio, K., Elluru, S.R., et al (2009 ) Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature 460: 1117–1121.
Not in our library10.1038/nature08264
9.
Alastruey‐Izquierdo, A., Mellado, E., and Cuenca‐Estrella, M. (2012 ) Current section and species complex concepts in Aspergillus: recommendations for routine daily practice. Ann N Y Acad Sci 1273: 18–24.
Not in our library10.1111/j.1749-6632.2012.06822.x
10.
Alastruey‐Izquierdo, A., Mellado, E., Peláez, T., Pemán, J., Zapico, S., Álvarez, M., et al (2013 ) Population‐based survey of filamentous fungi and antifungal resistance in Spain (FILPOP study). Antimicrob Agents Chemother 57: 3380–3387.
Not in our library10.1128/aac.00383-13
11.
Alborch, L., Bragulat, M.R., Abarca, M.I., and Cabañes, F.J. (2011 ) Effect of water activity, temperature and incubation time on growth and ochratoxin. A production by Aspergillus niger and Aspergillus carbonarius on maize kernels. Int J Food Microbiol 147: 53–57.
Not in our library10.1016/j.ijfoodmicro.2011.03.005
12.
Albrecht, D., Guthke, R., Brakhage, A.A., and Kniemeyer, O. (2010 ) Integrative analysis of the heat shock response in Aspergillus fumigatus. BMC Genom 11: 32–49.
Not in our library10.1186/1471-2164-11-32
13.
Allam, N.G., and Abd El‐Zaher, E.H.F. (2012 ) Protective role Aspergillus fumigatus melanin against ultraviolet (UV) irradiation and Bjerkandera adusta melanin as a candidate vaccine against systemic candidiasis. J Biotechnol 11: 6566–6577.
Not in our library
14.
Álvarez‐Pérez, S., Garcia, M.E., Bouza, E., Pelaez, T., and Blanco, J.L. (2009 ) Characterization of multiple isolates of Aspergillus fumigatus from patients: genotype, mating type and invasiveness. Med Mycol 47: 601–608.
Not in our library10.1080/13693780802380537
15.
Álvarez‐Pérez, S., Blanco, J.L., Alba, P., and Garcia, M.E. (2010a ) Mating type and invasiveness are significantly associated in Aspergillus fumigatus. Med Mycol 48: 273–277.
Not in our library10.1080/13693780903095414
16.
Álvarez‐Pérez, S., Blanco, J.L., Alba, P., and García, M.E. (2010b ) Sexualidad y patogenicidad en Aspergillus fumigatus: ¿existe alguna relación? Rev Iberoam Micol 27: 1–5.
Not in our library10.1016/j.riam.2009.11.005
17.
Álvarez‐Pérez, S., Mellado, E., Serrano, D., Blanco, J.L., García, M.E., Kwon, M., et al (2014 ) Polyphasic characterization of fungal isolates from a published case of invasive aspergillosis reveals misidentification of Aspergillus felis as Aspergillus viridinutans. J Med Microbiol 63: 617–619.
Not in our library10.1099/jmm.0.068502-0
18.
Alves, F.D.L., Stevenson, A., Baxter, E., Gillion, J.L., Hejazi, F., Morrison, I.E., et al (2015 ) Concomitant osmotic and chaotropicity‐induced stresses in Aspergillus wentii: compatible solutes determine the biotic window. Curr Genet 61: 457–477.
Not in our library10.1007/s00294-015-0496-8
19.
Amich, J., and Calera, J.A. (2014 ) Zinc acquisition: a key aspect in Aspergillus fumigatus virulence. Mycopathologia 178: 379–385.
Not in our library10.1007/s11046-014-9764-2
20.
Andersson, M.A., Nikulin, M., Koljalg, U., Andersson, M.C., Rainey, F., Reijula, K., et al (1997 ) Bacteria, molds, and toxins in water‐damaged building materials. Appl Environ Microbiol 63: 387–393.
Not in our library10.1128/aem.63.2.387-393.1997
21.
Arai, H. (2000 ) Foxing caused by fungi: twenty‐five years of study. Int Biodeter Biodegr 46: 181–188.
Not in our library
22.
Arriaga, S., Muñoz, R., Hernández, S., Guieysse, B., and Revah, S. (2006 ) Gaseous hexane biodegradation by Fusarium solani in two liquid phase packed‐bed and stirred‐tank bioreactors. Environ Sci Technol 40: 2390–2395.
Not in our library10.1021/es051512m
23.
Arvanitis, M., and Mylonakis, E. (2015 ) Diagnosis of invasive aspergillosis: recent developments and ongoing challenges. Eur J Clin Invest 45: 646–652.
Not in our library10.1111/eci.12448
24.
Askew, D.S. (2008 ) Aspergillus fumigatus: virulence genes in a street smart mold. Curr Opin Microbiol 11: 331–337.
Not in our library10.1016/j.mib.2008.05.009
25.
Babu, A. and Mitchell, J. (2015 ) Aspergilloma In Chest Surgery. Dienemann H.C., Hoffmann H. and Detterbeck F.C. (eds). Berlin Heidelberg: Springer, pp. 269–278.
Not in our library
26.
Baddley, J.W., Stroud, T.P., Salzman, D., and Pappas, P.G. (2001 ) Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis 32: 1319–1324.
Not in our library10.1086/319985
27.
Balajee, S.A., Gribskov, J.L., Hanley, E., Nickle, D., and Marr, K.A. (2005 ) Aspergillus lentulus sp. nov., a new sibling species of A. fumigatus. Eukaryot Cell 4: 625–632.
Not in our library10.1128/ec.4.3.625-632.2005
28.
Balajee, S.A., Baddley, J.W., Peterson, S.W., Nickle, D., Varga, J., Boey, A., et al (2009a ) Aspergillus alabamensis, a new clinically relevant species in the section Terrei. Eukaryot Cell 8: 713–722.
Not in our library10.1128/ec.00272-08
29.
Balajee, S.A., Kano, R., Baddley, J.W., Moser, S.A., Marr, K.A., Alexander, B.D., et al (2009b ) Molecular identification of Aspergillus species collected for the Transplant‐Associated Infection Surveillance Network. J Clin Microbiol 47: 3138–3141.
Not in our library10.1128/jcm.01070-09
30.
Ball, P., and Hallsworth, J.E. (2015 ) Water structure and chaotropicity: their uses, abuses and biological implications. Phys Chem Chem Phys 17: 8297–8305.
Not in our library10.1039/c4cp04564e
31.
Barnes, P.D., and Marr, K.A. (2006 ) Aspergillosis: spectrum of disease, diagnosis, and treatment. Infect Dis Clin North Am 20: 545–561.
Not in our library10.1016/j.idc.2006.06.001
32.
Aspergillus felis sp. nov., an emerging agent of invasive aspergillosis in humans, cats, and dogs. · 2013
Not checked
33.
Bart‐Delabesse, E., Marmorat‐Khuong, A., Costa, J.M., Dubreuil‐Lemaire, M.L., and Bretagne, S. (1997 ) Detection of Aspergillus DNA in bronchoalveolar lavage fluid of AIDS patients by the polymerase chain reaction. Eur J Clin Microbiol Infect Dis 16: 24–25.
Not in our library10.1007/bf01575116
34.
Beffa, T., Staib, F., Lott Fischer, J., Lyon, P.F., Gumowski, P., Marfenina, O.E., et al (1998 ) Mycological control and surveillance of biological waste and compost. Med Mycol 1: 137–145.
Not in our library
35.
Bekker, M., Huinink, H.P., Adan, O.C.G., Samson, R.A., Wyatt, T., and Dijksterhuis, J. (2012 ) Production of an extracellular matrix as an isotopic growth phase of Penicillium rubens on gypsum. Appl Environ Microbiol 78: 6930–6937.
Not in our library10.1128/aem.01506-12
36.
Bell, A.N.W., Magill, E., Hallsworth, J.E., and Timson, D.J. (2013 ) Effects of alcohols and compatible solutes on the activity of β‐galactosidase. Appl Biochem Biotechnol 169: 786–796.
Not in our library10.1007/s12010-012-0003-3
37.
Ben‐Ami, R., Lewis, R.E., Leventakos, K., and Kontoyiannis, D.P. (2009 ) Aspergillus fumigatus inhibits angiogenesis through the production of gliotoxin and other secondary metabolites. Blood 114: 5393–5399.
Not in our library10.1182/blood-2009-07-231209
38.
Bergmann, A., Hartmann, T., Cairns, T., Bignell, E.M., and Krappmann, S. (2009 ) A regulator of Aspergillus fumigatus extracellular proteolytic activity is dispensable for virulence. Infect Immun 77: 4041–4050.
Not in our library10.1128/iai.00425-09
39.
Beyenbach, K.W., and Wieczorek, H. (2006 ) The V‐type H+ ATPase: molecular structure and function, physiology and regulation. J Exp Biol 209: 577–589.
Not in our library10.1242/jeb.02014
40.
Bhabhra, R., and Askew, D.S. (2005 ) Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol 1: S87–S93.
Not in our library10.1080/13693780400029486
41.
Bhaganna, P., Volkers, R.J.M., Bell, A.N.W., Kluge, K., Timson, D.J., McGrath, J.W., et al (2010 ) Hydrophobic substances induce water stress in microbial cells. Microbial Biotechnol 3: 701–716.
Not in our library10.1111/j.1751-7915.2010.00203.x
42.
Bhaganna, P., Bielecka, A., Molinari, G., and Hallsworth, J.E. (2016 ) Protective role of glycerol against benzene stress; insights from the Pseudomonas putida proteome. Curr Genet 62(2): 419–429.
Not in our library10.1007/s00294-015-0539-1
43.
Binder, U., and Lass‐Flörl, C. (2013 ) New insights into invasive aspergillosis ‐ from the pathogen to the disease. Curr Pharm Des 19: 3679–3688.
Not in our library10.2174/13816128113199990366
44.
Blanco, J.L., Hontecillas, R., Bouza, E., Blanco, I., Pelaez, T., Munoz, P., et al (2002 ) Correlation between the elastase activity index and invasiveness of clinical isolates of Aspergillus fumigatus. J Clin Microbiol 40: 1811–1813.
Not in our library10.1128/jcm.40.5.1811-1813.2002
45.
Blum, G., Hörtnagl, C., Jukic, E., Erbeznik, T., Pümpel, T., Dietrich, H., et al (2013 ) New insight into amphotericin B resistance in Aspergillus terreus. Antimicrob Agents Chemother 57: 1583–1588.
Not in our library10.1128/aac.01283-12
46.
Border, D.J., Buck, K.W., Chain, E.B., Kempson‐Jones, G.F., Lhoas, P., and Ratti, G. (1972 ) Viruses of Penicillium and Aspergillus species. Biochem J 127: 4–6.
Not in our library10.1042/bj1270004p
47.
Comparative Secretome Analysis of Trichoderma reesei and Aspergillus niger during Growth on Sugarcane Biomass. · 2015
Not checked
48.
Bornstein, E., Hermans, W., Gridley, S., and Manni, J. (2009 ) Near‐infrared photoinactivation of bacteria and fungi at physiologic temperatures. Photochem Photobiol 85(6): 1364–1374.
Not in our library10.1111/j.1751-1097.2009.00615.x
49.
Bozza, S., Gaziano, R., Spreca, A., Bacci, A., Montagnoli, C., di Francesco, P., et al (2002 ) Dendritic cells transport conidia and hyphae of Aspergillus fumigatus from the airways to the draining lymph nodes and initiate disparate Th responses to the fungus. J Immunol 168: 1362–1371.
Not in our library10.4049/jimmunol.168.3.1362
50.
Calderone, R., Sun, N., Gay‐Andrieu, F., Groutas, W., Weerawarna, P., Prasad, S., et al (2014 ) Antifungal drug discovery: the process and outcomes. Future Microbiol 9: 791–805.
Not in our library10.2217/fmb.14.32
51.
Camps, S.M., Rijs, A.J., Klaassen, C.H., Meis, J.F., O'Gorman, C.M., Dyer, P.S., et al (2012 ) Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism. J Clin Microbiol 50: 2674–2680.
Not in our library10.1128/jcm.00335-12
52.
Cannon, R.D., Lamping, E., Holmes, A.R., Niimi, K., Baret, P.V., Keniya, M.V., et al (2009 ) Efflux‐mediated antifungal drug resistance. Clin Microbiol Rev 22: 291–321.
Not in our library10.1128/cmr.00051-08
53.
Chang, Y.C., Tsai, H.F., Karos, M., and Kwon‐Chung, K.J. (2004 ) THTA, a thermotolerance gene of Aspergillus fumigatus. Fungal Genet Biol 41: 888–896.
Not in our library10.1016/j.fgb.2004.06.004
54.
Cheema, M.S., and Christians, J.K. (2011 ) Virulence in an insect model differs between mating types in Aspergillus fumigatus. Med Mycol 49: 202–207.
Not in our library10.3109/13693786.2010.512301
55.
Chen, S.C., Slavin, M.A., and Sorrell, T.C. (2011 ) Echinocandin antifungal drugs in fungal infections: a comparison. Drugs 71: 11–41.
Not in our library10.2165/11585270-000000000-00000
56.
Chin, J.P., Megaw, J., Magill, C.L., Nowotarski, K., Williams, J.P., Bhaganna, P., et al (2010 ) Solutes determine the temperature windows for microbial survival and growth. Proc Natl Acad Sci USA 107: 7835–7840.
Not in our library10.1073/pnas.1000557107
57.
Coelho, D., Silva, S., Vale‐Silva, L., Gomes, H., Pinto, E., Sarmento, A., et al (2011 ) Aspergillus viridinutans: an agent of adult chronic invasive aspergillosis. Med Mycol 49: 755–759.
Not in our library10.3109/13693786.2011.556672
58.
Coenen, A., Kevei, F., and Hoekstra, R.F. (1997 ) Factors affecting the spread of double‐stranded RNA viruses in Aspergillus nidulans. Genet Res 69: 1–10.
Not in our library10.1017/s001667239600256x
59.
Cramer, R.A., Rivera, A., and Hohl, T.M. (2011 ) Immune responses against Aspergillus fumigatus: what have we learned? Curr Opin Infect Dis 24: 315–322.
Not in our library10.1097/qco.0b013e328348b159
60.
The biology of habitat dominance; can microbes behave as weeds? · 2013
No notice
61.
Cray, J.A., Russell, J.T., Timson, D.J., Singhal, R.S., and Hallsworth, J.E. (2013b ) A universal measure of chaotropicity and kosmotropicity. Environ Microbiol 15: 287–296.
Not in our library10.1111/1462-2920.12018
62.
Cray, J.A., Bhaganna, P., Singhal, R.S., Patil, S.V., Saha, D., Chakraborty, R., et al (2014 ) Chaotropic and hydrophobic stress mechanisms of antifungal substances In Modern Fungicides and Antifungal Compounds, vol. VII. Dehne H.W., Deising H.B., Fraaije B., Gisi U., Hermann D., Mehl A., Oerke E.C., Russell P.E., Stammler G., Kuck K.H. and Lyr H. (eds). Braunschweig, Germany: Deutsche Phytomedizinische Gesellschaft, ISBN: 978‐3‐941261‐13‐6.
Not in our library
63.
Cray, J.A., Stevenson, A., Ball, P., Bankar, S.B., Eleutherio, E.C., Ezeji, T.C., et al (2015a ) Chaotropicity: a key factor in product tolerance of biofuel‐producing microorganisms. Curr Opin Biotechnol 33: 258–259.
Not in our library10.1016/j.copbio.2015.02.010
64.
Cray, J.A., Houghton, J.D., Cooke, L.R., and Hallsworth, J.E. (2015b ) A simple inhibition coefficient for quantifying potency of biocontrol agents against plant‐pathogenic fungi. Biol Control 81: 93–100.
Not in our library
65.
Cray, J.A., Connor, M.C., Stevenson, A., Houghton, J.D.R., Rangel, D.E.N., Cooke, L.R., et al (2016 ) Biocontrol agents promote growth of potato pathogens, depending on environmental conditions. Microbial Biotechnol 9: 330–354.
Not in our library10.1111/1751-7915.12349
66.
Crowe, J.H., Crowe, L.M., and Chapman, D. (1984 ) Preservation of membranes in anhydrobiotic organisms – the role of trehalose. Science 223: 701–703.
Not in our library10.1126/science.223.4637.701
67.
Dadachova, E., and Casadevall, A. (2008 ) Ionizing radiation: how fungi cope, adapt, and exploit with the help of melanin. Curr Opin Microbiol 11: 525–531.
Not in our library10.1016/j.mib.2008.09.013
68.
Dagenais, T.R., and Keller, N.P. (2009 ) Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clin Microbiol Rev 22: 447–465.
Not in our library10.1128/cmr.00055-08
69.
da Silva, M.T.S., Soares, C.M.F., Lima, A.S., and Santana, C.C. (2015 ) Integral production and concentration of surfactin from Bacillus sp. ITP‐001 by semi‐batch foam fractionation. Biochem Eng J 104: 91–97.
Not in our library
70.
De Pauw, B., Walsh, T.J., Donnelly, J.P., Stevens, D.A., Edwards, J.E., Calandra, T., et al (2008 ) Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 46: 1813–1821.
Not in our library10.1086/588660
71.
The Airway Microbiota in Cystic Fibrosis: A Complex Fungal and Bacterial Community—Implications for Therapeutic Management · 2012
No notice
72.
Denning, D.W. (1996 ) Therapeutic outcome in invasive aspergillosis. Clin Infect Dis 23: 608–614.
Not in our library10.1093/clinids/23.3.608
73.
Denning, D.W., and Perlin, D.S. (2011 ) Azole resistance in Aspergillus: a growing public health menace. Future Microbiol 6: 1229.
Not in our library10.2217/fmb.11.118
74.
Fungal allergy in asthma–state of the art and research needs · 2014
No notice
75.
Diamond, R.D., and Clark, R.A. (1982 ) Damage to Aspergillus fumigatus and Rhizopus oryzae hyphae by oxidative and nonoxidative microbicidal products of human neutrophils in vitro. Infect Immun 38: 487–495.
Not in our library10.1128/iai.38.2.487-495.1982
76.
Exploring temporal transcription regulation structure of <it>Aspergillus fumigatus </it>in heat shock by state space model · 2009
Not checked
77.
Drakos, P.E., Nagler, A., Or, R., Naparstek, E., Kapelushnik, J., Engelhard, D., et al (1993 ) Invasive fungal sinusitis in patients undergoing bone marrow transplantation. Bone Marrow Transplant 12: 203–208.
Not in our library
78.
Duran, R., Cary, J.W., and Calvo, A.M. (2010 ) Role of the osmotic stress regulatory pathway in morphogenesis and secondary metabolism in filamentous fungi. Toxins 2: 367–381.
Not in our library10.3390/toxins2040367
79.
Dyer, P.S., and O'Gorman, C.M. (2012 ) Sexual development and cryptic sexuality in fungi: insights from Aspergillus species. FEMS Microbiol Rev 36: 165–192.
Not in our library10.1111/j.1574-6976.2011.00308.x
80.
Dyer, P.S., and Paoletti, M. (2005 ) Reproduction in Aspergillus fumigatus: sexuality in a supposedly asexual species? Med Mycol 1: S7–S14.
Not in our library10.1080/13693780400029015
81.
Ellis, D. (2002 ) Amphotericin B: spectrum and resistance. Antimicrob Agents Chemother 49: 7–10.
Not in our library10.1093/jac/49.suppl_1.7
82.
Ellis, J.J., and Roberson, J.A. (1968 ) Viability of fungus cultures preserved by lyophilization. Mycologia 60: 399–405.
Not in our library
83.
Enoch, D.A., Ludlam, H.A., and Brown, N.M. (2006 ) Invasive fungal infections: a review of epidemiology and management options. J Med Microbiol 55: 809–818.
Not in our library10.1099/jmm.0.46548-0
84.
Escribano, P., Peláez, T., Bouza, E., and Guinea, J. (2015 ) Microsatellite (STRAf) genotyping cannot differentiate between invasive and colonizing Aspergillus fumigatus isolates. J Clin Microbiol 53: 667–670.
Not in our library10.1128/jcm.02636-14
85.
Fairs, A., Agbetile, J., Bourne, M., Hargadon, B., Monteiro, W.R., Morley, J.P., et al (2013 ) Isolation of Aspergillus fumigatus from sputum is associated with elevated airborne levels in homes of patients with asthma. Indoor Air 23: 275–284.
Not in our library10.1111/ina.12020
86.
Fang, F.C. (1997 ) Mechanisms of nitric oxide‐related antimicrobial activity. J Clin Invest 99: 2818–2825.
Not in our library10.1172/jci119473
87.
Fungal Biofilms · 2012
No notice
88.
Ferreira, J.A.G., Penner, J.C., Moss, R.B., Haagensen, J.A.J., Clemons, K.V., Spormann, A.M., et al (2015 ) Inhibition of Aspergillus fumigatus and its biofilm by Pseudomonas aerugenosa is dependent on the source, phenotype and growth conditions of the bacterium. PLoS ONE 10: e0134692.
Not in our library10.1371/journal.pone.0134692
89.
Ferrer, M., Chernikova, T.N., Yakimov, M.M., Golyshin, P.N., and Timmis, K.N. (2003 ) Chaperonins govern growth of Escherichia coli at low temperatures. Nat Biotechnol 21: 1266–1267.
Not in our library10.1038/nbt1103-1266
90.
Fields, P.A. (2001 ) Review: Protein function at thermal extremes: balancing stability and flexibility. Comp Biochem Physiol A Mol Integr Physiol 129: 417–431.
Not in our library10.1016/s1095-6433(00)00359-7
91.
Fungal Invasion of Normally Non-Phagocytic Host Cells · 2006
No notice
92.
Flewelling, A.J., Bishop, A.I., Johnson, J.A., and Gray, C.A. (2015 ) Polyketides from an endophytic Aspergillus fumigatus isolate inhibit the growth of Mycobacterium tuberculosis and MRSA. Nat Prod Commun 10: 1661–1662.
Not in our library
93.
Flipphi, M., Sunb, J., Robelletc, X., Karaffad, L., Feketed, E., Zengb, A.P., et al (2009 ) Biodiversity and evolution of primary carbon metabolism in Aspergillus nidulans and other Aspergillus spp. Fungal Genet Biol 46: S19–S44.
Not in our library10.1016/j.fgb.2008.07.018
94.
Fox‐Powell, M.G., Hallsworth, J.E., Cousins, C.R. and Cockell, C.S. (in press) Ionic strength is a barrier to the habitability of Mars. Astrobiology.
Not in our library10.1089/ast.2015.1432
95.
Freitas, J.S., Silva, E.M., Leal, J., Gras, D.E., Martinez‐Rossi, N.M., dos Santos, L.D., et al (2011 ) Transcription of the Hsp30, Hsp70, and Hsp90 heat shock protein genes is modulated by the PalA protein in response to acid pH‐sensing in the fungus Aspergillus nidulans. Cell Stress Chaperones 16: 565–572.
Not in our library10.1007/s12192-011-0267-5
96.
Fritzler, J.M., Millership, J.J., and Zhu, G. (2007 ) Cryptosporidium parvum long‐chain fatty acid enlongase. Eukaryot Cell 6: 2018–2028.
Not in our library10.1128/ec.00210-07
97.
Gaetke, L.M., and Chow, C.K. (2003 ) Copper toxicity, oxidative stress, and antioxidant nutrients. Toxicology 189: 147–163.
Not in our library10.1016/s0300-483x(03)00159-8
98.
Genome Sequencing and Comparative Transcriptomics of the Model Entomopathogenic Fungi Metarhizium anisopliae and M. acridum · 2011
No notice
99.
Gomez, B.L. (2014 ) Molecular diagnosis of endemic and invasive mycoses: advances and challenges. Rev Iberoam Micol 31: 35–41.
Not in our library10.1016/j.riam.2013.09.009
100.
Gonçalves, S.S., Stchigel, A.M., Cano, J.F., Godoy‐Martinez, P.C., Colombo, A.L., and Guarro, J. (2012 ) Aspergillus novoparasiticus: a new clinical species of the section Flavi. Med Mycol 50: 152–160.
Not in our library10.3109/13693786.2011.593564
101.
Graü, C., Sánchez, D., Zerpa, A., and García, N. (2007 ) Influence of water activity, pH, and temperature on growth of Aspergillus penicillioides and A. terreus, isolated from dry and salted skipjack tuna (Katsuwonus pelamis) meat. Revista Científica 17: 193–199.
Not in our library
102.
Greer, N.D. (2003 ) Voriconazole: the newest triazole antifungal agent. Proc (Bayl Univ Med Cent) 16: 241–248.
Not in our library10.1080/08998280.2003.11927910
103.
A polysaccharide virulence factor from Aspergillus fumigatus elicits anti-inflammatory effects through induction of Interleukin-1 receptor antagonist. · 2014
Not checked
104.
Grum‐Grzhimaylo, A.A., Georgieva, M.L.M., Bondarenko, S.A., Debets, A.J.M., and Bilanenko, E.N. (2015 ) On the diversity of fungi from soda soils. Fungal Divers 76: 27–74.
Not in our library
105.
Gugnani, H.C. (2003 ) Ecology and taxonomy of pathogenic aspergilli. Front Biosci 8: 346–357.
Not in our library10.2741/1002
106.
Gupta, K., Gupta, P., Mathew, J.L., Bansal, A., Singh, G., Singh, M., et al (in press) Fatal disseminated Aspergillus penicillioides infection in a three‐month‐old infant with suspected cystic fibrosis: autopsy case with review of literature. Pediatr Dev Pathol. doi:10.2350/15‐10‐1729‐CR.1.
Not in our library10.2350/15-10-1729-cr.1
107.
Haas, H. (2012 ) Iron ‐ A key nexus in the virulence of Aspergillus fumigatus. Front Microbiol 3: 28.
Not in our library10.3389/fmicb.2012.00028
108.
Hall, L.A., and Denning, D.W. (1994 ) Oxygen requirements of Aspergillus species. J Med Microbiol 41: 311–315.
Not in our library10.1099/00222615-41-5-311
109.
Hall, D., and Hoshino, M. (2010 ) Effects of macromolecular crowding on intracellular diffusion from a single particle perspective. Biophys Rev 2: 39–53.
Not in our library10.1007/s12551-010-0029-0
110.
Hallsworth, J.E., and Magan, N. (1994 ) Effect of carbohydrate type and concentration on polyols and trehalose in conidia of three entomopathogenic fungi. Microbiology 140: 2705–2713.
Not in our library
111.
Hallsworth, J.E., and Magan, N. (1995 ) Manipulation of intracellular glycerol and erythritol enhances germination of conidia at low water availability. Microbiology 141: 1109–1115.
Not in our library10.1099/13500872-141-5-1109
112.
Hallsworth, J.E., Heim, S., and Timmis, K.N. (2003a ) Chaotropic solutes cause water stress in Pseudomonas putida. Environ Microbiol 5: 1270–1280.
Not in our library10.1111/j.1462-2920.2003.00478.x
113.
Hallsworth, J.E., Prior, B.A., Nomura, Y., Iwahara, M., and Timmis, K.N. (2003b ) Compatible solutes protect against chaotrope (ethanol)‐induced, nonosmotic water stress. Appl Environ Microbiol 69: 7032–7034.
Not in our library10.1128/aem.69.12.7032-7034.2003
114.
Hallsworth, J.E., Yakimov, M.M., Golyshin, P.N., Gillion, J.L.M., D'Auria, G., Alves, F.L., et al (2007 ) Limits of life in MgCl2‐containing environments: chaotropicity defines the window. Environ Microbiol 9: 803–813.
Not in our library10.1111/j.1462-2920.2006.01212.x
115.
Hashimoto, K., Kagami, K., Yokoyama, K., Fukuda, A., and Kawakami, Y. (2010 ) Identification of Aspergillus section Restrictus group isolated from the art museum, by gene analysis and morphological observation. Indoor Environ 13: 131–139.
Not in our library
116.
Hedayati, M.T., Pasqualotto, A.C., Warn, P.A., Bowyer, P., and Denning, D.W. (2007 ) Aspergillus flavus: human pathogen, allergen and mycotoxin producer. Microbiology 153: 1677–1692.
Not in our library10.1099/mic.0.2007/007641-0
117.
Heitman, J., Carter, D.A., Dyer, P.S., and Soll, D.R. (2014 ) Sexual reproduction of human fungal pathogens. Cold Spring Harb Perspect Med 4: a019281.
Not in our library10.1101/cshperspect.a019281
118.
Hesseltine, C.W., and Rogers, R.F. (1982 ) Longevity of Aspergillus flavus in corn. Mycologia 74: 423–426.
Not in our library
119.
Hillmann, F., Novohradska, S., Mattern, D.J., Forberger, T., Heinekamp, T., Westermann, M., et al (2015a ) Virulence determinants of the human pathogenic fungus Aspergillus fumigatus protect against soil amoeba predation. Environ Biol 17: 2858–2869.
Not in our library10.1111/1462-2920.12808
120.
Hillmann, F., Shekhova, E., and Kniemeyer, O. (2015b ) Insights into the cellular responses to hypoxia in filamentous fungi. Curr Genet 61: 441–455.
Not in our library10.1007/s00294-015-0487-9
121.
Hocking, A.D. (1993 ) Responses of xerophilic fungi to changes in water activity In Stress Tolerance of Fungi. Jennings D.H. (ed). New York: Marcel Decker, pp. 233–256.
Not in our library
122.
Hogan, L.H., Klein, B.S., and Levitz, S.M. (1996 ) Virulence factors of medically important fungi. Clin Microbiol Rev 9: 469–488.
Not in our library10.1128/cmr.9.4.469
123.
Horn, B.W., Moore, G.G., and Carbone, I. (2009a ) Sexual reproduction in Aspergillus flavus. Mycologia 101: 423–429.
Not in our library10.3852/09-011
124.
Horn, B.W., Ramirez‐Prado, J.H., and Carbone, I. (2009b ) The sexual state of Aspergillus parasiticus. Mycologia 101: 275–280.
Not in our library10.3852/08-205
125.
Houbraken, J., de Vries, R.P., and Samson, R.A. (2014 ) Modern taxonomy of biotechnologically important Aspergillus and Penicillium species. Adv Appl Microbiol 86: 199–249.
Not in our library10.1016/b978-0-12-800262-9.00004-4
126.
Houbraken, J., Weig, M., Groß, U., Meijer, M. and Bader, O. (2016 ) Aspergillus oerlinghausenensis, a new mould species closely related to A. fumigatus. FEMS Microbiol Lett 363: Fnv236.
Not in our library10.1093/femsle/fnv236
127.
Howard, S.J. (2014 ) Multi‐resistant aspergillosis due to cryptic species. Mycopathologia 178: 435–439.
Not in our library10.1007/s11046-014-9774-0
128.
Ja'afaru, M.I. and Fagade, O.E. (2010 ) Optimization studies on cellulose enzyme production by an isolated strain of Aspergillus niger YL128. Afr J Microbiol Res 4: 2635–2639.
Not in our library
129.
Jahn, B., Koch, A., Schmidt, A., Wanner, G., Gehringer, H., Bhakdi, S., et al (1997 ) Isolation and characterization of a pigmentless‐conidium mutant of Aspergillus fumigatus with altered conidial surface and reduced virulence. Infect Immun 65: 5110–5117.
Not in our library10.1128/iai.65.12.5110-5117.1997
130.
James, P.E., Madani, M., Ross, C., Klei, L., Barchowsky, A., and Swartz, H.M. (2003 ) Tissue hypoxia during bacterial sepsis is attenuated by PR‐39, an antibacterial peptide. Adv Med Biol 530: 645–652.
Not in our library10.1007/978-1-4615-0075-9_64
131.
Jarosławiecka, A., and Piotrowska‐Seget, Z. (2014 ) Lead resistance in micro‐organisms. Microbiology 160: 12–25.
Not in our library10.1099/mic.0.070284-0
132.
Jernejc, K., and Legiš, M. (2004 ) A drop of intracellular pH stimulates citric acid accumulation by some strains of Aspergillus niger. J Biotech 112: 289–297.
Not in our library10.1016/j.jbiotec.2004.05.002
133.
Jin, Y., Weining, S., and Nevo, E. (2005 ) A MAPK gene from Dead Sea fungus confers stress tolerance to lithium salt and freeze‐thawing: prospects for saline agriculture. Proc Natl Acad Sci USA 102: 18992–18997.
Not in our library10.1073/pnas.0509653102
134.
Jørgensen, T.R., Nielson, K.F., Arentshorst, M., Park, J., van den Hondel, C.A., Frisvad, J.C., et al (2011 ) Submerged conidiation and product formation by Aspergillus niger at low specific growth rates are affected in aerial developmental mutants. Appl Environ Microbiol 77: 5270–5277.
Not in our library10.1128/aem.00118-11
135.
Kamei, K., and Watanabe, A. (2005 ) Aspergillus mycotoxins and their effect on the host. Med Mycol 1: S95–S99.
Not in our library10.1080/13693780500051547
136.
Kashangura, C., Hallsworth, J.E., and Mswaka, A.Y. (2006 ) Phenotypic diversity amongst strains of Pleurotus sajor‐caju: implications for cultivation in arid environments. Mycol Res 110: 312–317.
Not in our library10.1016/j.mycres.2005.10.006
137.
Kauffman, H.F. (2003 ) Immunopathogenesis of allergic bronchopulmonary aspergillosis and airway remodeling. Front Biosci 8: e190–e196.
Not in our library10.2741/990
138.
Kaur, S., and Singh, S. (2014 ) Biofilm formation by Aspergillus fumigatus. Med Mycol 52: 2–9.
Not in our library10.3109/13693786.2013.819592
139.
Kilikian, B.V., and Jurkiewicz, C.H. (1997 ) The gas balance technique and the respiratory coefficient variability in cultures of Aspergillus awamori NRRL 3112. Braz J Chem Eng 14: 113–118.
Not in our library
140.
Klaassen, C.H., Gibbons, J.G., Fedorova, N.D., Meis, J.F., and Rokas, A. (2012 ) Evidence for genetic differentiation and variable recombination rates among Dutch populations of the opportunistic human pathogen Aspergillus fumigatus. Mol Ecol 21: 57–70.
Not in our library10.1111/j.1365-294x.2011.05364.x
141.
Knuf, C., and Nielsen, J. (2012 ) Aspergilli: systems biology and industrial applications. Biotechnol J 7: 1147–1155.
Not in our library10.1002/biot.201200169
142.
Ko, S.S., Huang, J.W., Wang, J.F., Shanmugasundaram, S., and Chang, W.N. (2002 ) Evaluation of onion cultivars for resistance to Aspergillus niger, the causal agent of black mould. J Am Soc Hortic Sci 127: 697–702.
Not in our library
143.
Kolwijck, E., and van de Veerdonk, F.L. (2014 ) The potential impact of pulmonary microbiome on immunopathogenesis of Aspergillus‐related lung disease. Eur J Immunol 44: 3156–3165.
Not in our library10.1002/eji.201344404
144.
Kosmidis, C., and Denning, D.W. (2015a ) The clinical spectrum of pulmonary aspergillosis. Thorax 70: 270–277.
Not in our library10.1136/thoraxjnl-2014-206291
145.
Kosmidis, C., and Denning, D.W. (2015b ) Republished: the clinical spectrum of pulmonary aspergillosis. Postgrad Med J 91: 403–410.
Not in our library10.1136/postgradmedj-2014-206291rep
146.
Kothary, M.H., Chase, T. Jr, and Macmillan, J.D. (1984 ) Correlation of elastase production by some strains of Aspergillus fumigatus with ability to cause pulmonary invasive aspergillosis in mice. Infect Immun 43: 320–325.
Not in our library10.1128/iai.43.1.320-325.1984
147.
Kraemer, R., Delose'a, N., Ballinari, P., Gallati, S., and Crameri, R. (2006 ) Effect of allergic bronchopulmonary aspergillosis on lung function in children with cystic fibrosis. Am J Respir Crit Care Med 174: 1211–1220.
Not in our library10.1164/rccm.200603-423oc
148.
Krijgsheld, P., Altelaar, A.F., Post, H., Ringrose, J.H., Müller, W.H., Heck, A.J., and Wösten, H.A. (2012 ) Spatially resolving the secretome within the mycelium of the cell factory Aspergillus niger. J Proteome Res 11: 2807–2818.
Not in our library10.1021/pr201157b
149.
Krohn, N.G., Brown, N.A., Colabardini, A.C., Reis, T., Savoldi, M., Dinamarco, T.M., et al (2014 ) The Aspergillus nidulans ATM kinase regulates mitochondrial function, glucose uptake and the carbon starvation response. G3: Genes ‐ Genomes ‐ Genetics 4: 49–62.
Not in our library10.1534/g3.113.008607
150.
Kroll, K., Pähtz, V., Hilmann, F., Vaknin, Y., Schmidt‐Heck, W., Roth, M., et al (2014 ) Indentification of hypoxia‐ inducible target genes of Aspergillus fumigatus by transcriptome analysis reveals cellular respiration as an important contributor to hypoxic survival. Eukaryot Cell 13: 1241–1253.
Not in our library10.1128/ec.00084-14
151.
Kroll, K., Shekhova, E., Mattern, D.J., Thywissen, A., Jacobsen, I.D., Strassburger, M., et al (in press) The hypoxia‐induced dehydrogenase HorA is required for coenzyme Q10 biosynthesis, azole sensitivity and virulence of Aspergillus fumigatus. Mol Microbiol. doi:10.1111/mmi.13377.
Not in our library10.1111/mmi.13377
152.
Aspergillus fumigatus—What Makes the Species a Ubiquitous Human Fungal Pathogen? · 2013
No notice
153.
Lackner, M., and Lass‐Flörl, C. (2013 ) Up‐date on diagnostic strategies of invasive aspergillosis. Curr Pharm Des 19: 3595–3614.
Not in our library10.2174/13816128113199990323
154.
Lamarre, C., Sokol, S., Debeaupuis, J.P., Henry, C., Lacroix, C., Glaser, P., et al (2008 ) Transcriptomic analysis of the exit from dormancy of Aspergillus fumigatus conidia. BMC Genom 9: 417–432.
Not in our library10.1186/1471-2164-9-417
155.
Lamoth, F., Juvvadi, P.R., Fortwendel, J.R., and Steinbach, W.J. (2012 ) Heat shock protein 90 is required for conidiation and cell wall integrity in Aspergillus fumigatus. Eukaryot Cell 11: 1324–1332.
Not in our library10.1128/ec.00032-12
156.
Lamoth, F., Juvvadi, P.R., and Steinbach, W.J. (2014 ) Heat shock protein 90 (Hsp90): a novel antifungal target against Aspergillus fumigatus. Crit Rev Microbiol 22: 1–12.
Not in our library10.3109/1040841x.2014.947239
157.
Lass‐Flörl, C., Griff, K., Mayr, A., Petzer, A., Gastl, G., Bonatti, H., et al (2005 ) Epidemiology and outcome of infections due to Aspergillus terreus: 10‐year single centre experience. Br J Haematol 131: 201–207.
Not in our library10.1111/j.1365-2141.2005.05763.x
158.
Lass‐Flörl, C. (2012 ) Aspergillus terreus: how inoculum size and host characteristics affect its virulence. J Infect Dis 205: 1268–1277.
Not in our library10.1093/infdis/jis185
159.
Latgé, J.P. (1999 ) Aspergillus fumigatus and aspergillosis. Clin Microbiol Rev 12: 310–350.
Not in our library10.1128/cmr.12.2.310
160.
Latgé, J.P. (2001 ) The pathobiology of Aspergillus fumigatus. Trends Microbiol 9: 382–389.
Not in our library10.1016/s0966-842x(01)02104-7
161.
Lee, S.C., Ni, M., Li, W., Shertz, C., and Heitman, J. (2010 ) The evolution of sex: a perspective from the fungal kingdom. Microbiol Mol Biol Rev 74: 298–340.
Not in our library10.1128/mmbr.00005-10
162.
van Leeuwen, M.R., Wyatt, T.T., van Doorn, T.M., Lugones, L.G., Wösten, H.A.B., and Diijksterhuis, J. (2016 ) Hydrophilins in the filamentous fungus Neosartorya fischeri (Aspergillus fischeri) have protective activity against several types of microbial water stress. Environ Microbiol Rep 8: 45–52.
Not in our library10.1111/1758-2229.12349
163.
Lewis, J.S., Lee, J.A., Underwood, J.C., Harris, A.L., and Lewis, C.E. (1999 ) Macrophage responses to hypoxia: relevance to disease mechanisms. J Leukoc Biol 66: 889–900.
Not in our library10.1002/jlb.66.6.889
164.
Lievens, B., Rep, M., and Thomma, B.P.H.J. (2008 ) Recent developments in the molecular discrimination of formae speciales of Fusarium oxysporum. Pest Manag Sci 64: 781–788.
Not in our library10.1002/ps.1564
165.
Lievens, B., Hallsworth, J.E., Belgacem, Z.B., Pozo, M.I., Stevenson, A., Willems, K.A., and Jacquemyn, H. (2015 ) Microbiology of sugar‐rich environments: diversity, ecology, and system constraints. Environ Microbiol 17: 278–298.
Not in our library10.1111/1462-2920.12570
166.
Lin, X., Huang, J.C., Mitchell, T.G., and Heitman, J. (2006 ) Virulence attributes and hyphal growth of C. neoformans are quantitative traits and the MATα allele enhances filamentation. PLoS Genet 2: e187.
Not in our library10.1371/journal.pgen.0020187
167.
Longworthy, T.A. (1978 ) Microbial life in extreme pH values In Microbial Life in Extreme Environments. Kushner D.J. (ed). London: Academic Press, pp. 279–315.
Not in our library
168.
Lopes Bezerra, L.M., and Filler, S.G. (2004 ) Interactions of Aspergillus fumigatus with endothelial cells: internalization, injury and stimulation of tissue factor activity. Blood 103: 2143–2349.
Not in our library10.1182/blood-2003-06-2186
169.
Lortholary, O., Guillevin, L., and Dupont, B. (1995 ) Manifestations extrapulmonaires de l'aspergillose invasive. Ann Med Interne 146: 96–101.
Not in our library
170.
Losada, L., Ajayi, O., Frisvas, J.C., Yu, J. and Nierman, W.C. (2009 ) Effect of competition on the production and activity of secondary metabolites in Aspergillus species. Med Mycol 47: S88–S96.
Not in our library10.1080/13693780802409542
171.
Losada, L., Sugui, J.A., Eckhaus, M.A., Chang, Y.C., Mounaud, S., Figat, A., et al (2015 ) genetic analysis using an isogenic mating pair of Aspergillus fumigatus identifies azole resistance genes and lack of MAT locus's role in virulence. PLoS Pathog 11: e1004834.
Not in our library10.1371/journal.ppat.1004834
172.
Lozupone, C.A., Stombaugh, J.I., Gordon, J.I., Jansson, J.K., and Knight, R. (2012 ) Diversity, stability and resilience of the human gut microbiota. Nature 489: 220–230.
Not in our library10.1038/nature11550
173.
Ludwig, N., Löhrer, M., Hempel, M., Mathea, S., Schliebner, I., Menzel, M., et al (2014 ) Melanin is not required for turgor generation but enhance cell‐wall rigidity in appressoria of corn pathogen Collectotrichum graminicola. Mol Plant Microbe Interact 4: 315–327.
Not in our library10.1094/mpmi-09-13-0267-r
174.
Lui, X., Wei, Y., Zhou, X., Pei, X., and Zhang, S. (2015 ) The Aspergillus aquaglyceroporin gene AgGlpF confers high osmosis tolerance in heterologous organisms. Appl Environ Microbiol 81: 6926–6937.
Not in our library10.1128/aem.02127-15
175.
Luna, M.A.C., Vieira, E.R., Okada, K., Campos‐Takaki, G.B., and do Nascimento, A.E. (2015 ) Copper‐induced adaptation, oxidative stress and its tolerance in Aspergillus niger UCP1261. Biotechnology 18: 418–427.
Not in our library
176.
Ma, D., and Li, R. (2013 ) Current understanding of HOG‐MAPK pathway in Aspergillus fumigatus. Mycopathologia 175: 13–23.
Not in our library10.1007/s11046-012-9600-5
177.
Maschmeyer, G., Haas, A., and Cornely, O.A. (2007 ) Invasive aspergillosis: epidemiology, diagnosis and management in immunocompromised patients. Drugs 67: 1567–1601.
Not in our library10.2165/00003495-200767110-00004
178.
Maturu, V.N., and Agarwal, R. (2015 ) Prevalence of Aspergillus sensitization and allergic bronchopulmonary aspergillosis in cystic fibrosis: systematic review and meta‐analysis. Clin Exp Allergy 45: 1765–1778.
Not in our library10.1111/cea.12595
179.
McCammick, E.M., Gomase, V.S., Timson, D.J., McGenity, T.J. and Hallsworth, J.E. (2010 ) Water‐hydrophobic compound interactions with the microbial cell In Handbook of Hydrocarbon and Lipid Microbiology – Hydrocarbons, Oils and Lipids: Diversity, Properties and Formation, Vol. 2. Timmis K.N. (ed.). New York: Springer, pp. 1451–1466.
Not in our library
180.
Mehl, H.L., and Cotty, P.J. (2010 ) Variation in competitive ability among isolates of Aspergillus flavus from different vegetative compatibility groups during maize infection. Mycology 100: 150–159.
Not in our library10.1094/phyto-100-2-0150
181.
Mehl, H.L., and Cotty, P.J. (2011 ) Influence of the host contact sequence on the outcome of competition among Aspergillus flavus isolates during host tissue invasion. Appl Environ Microbiol 77: 1691–1697.
Not in our library10.1128/aem.02240-10
182.
Mehl, H.L., and Cotty, P.J. (2013 ) Influence of plant host species on intraspecific competition during infection by Aspergillus flavus. Plant Pathol 62: 1310–1318.
Not in our library
183.
Mellon, J.E., Cotty, P.J., and Dowd, M.K. (2007 ) Aspergillus flavus hydrolases: their roles in pathogenesis and substrate utilization. Appl Microbiol Biotechnol 77: 497–450.
Not in our library10.1007/s00253-007-1201-8
184.
Middlebrooks, E.H., Frost, C.J., De Jesus, R.O., Massini, T.C., Schmalfuss, I.M., and Mancuso, A.A. (2015 ) Acute invasive fungal rhinosinusitis: a comprehensive update of CT findings and design of an effective diagnostic imaging model. Am J Neuroradiol 36: 1529–1535.
Not in our library10.3174/ajnr.a4298
185.
Mira, N.P., Teixeira, M.C., and Sá‐Correia, I. (2010 ) Adaptive response and tolerance to weak acids in Saccharomyces cerevisiae: a genomic‐wide view. OMICS 14: 525–540.
Not in our library10.1089/omi.2010.0072
186.
Missall, T.A., Lodge, J.K., and McEwen, J.E. (2004 ) Mechanisms of resistance to oxidative and nitrosative stress implications for fungal survival in mammalian hosts. Eukaryot Cell 3: 835–846.
Not in our library10.1128/ec.3.4.835-846.2004
187.
Mitchell, C.G., Slight, J., and Donaldson, K. (1997 ) Diffusible component from the spore surface of the fungus Aspergillus fumigatus which inhibits the macrophage oxidative burst is distinct from gliotoxin and other hyphal toxins. Thorax 52: 796–801.
Not in our library10.1136/thx.52.9.796
188.
Moreno, M.A., Ibrahim‐Granet, O., Vicentefranqueira, R., Amich, J., Ave, P., Leal, F., et al (2007 ) The regulation of zinc homeostasis by the ZafA transcriptional activator is essential for Aspergillus fumigatus virulence. Mol Microbiol 64: 1182–1197.
Not in our library10.1111/j.1365-2958.2007.05726.x
189.
Morrison, B.E., Park, S.J., Mooney, J.M., and Mehrad, B. (2003 ) Chemokine‐mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis. J Clin Invest 112: 1862–1870.
Not in our library10.1172/jci18125
190.
Morrissey, C.O., Chen, S.C., Sorrell, T.C., Milliken, S., Bardy, P.G., Bradstock, K.F., et al (2013 ) Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high‐risk haematology patients: a randomised controlled trial. Lancet Infect Dis 13: 519–528.
Not in our library10.1016/s1473-3099(13)70076-8
191.
Mowat, E., Rajendran, R., Williams, C., McCulloch, E., Jones, B., Lang, S., et al (2010 ) Pseudomonas aeruginosa and their small diffusible extracellular molecules inhibit Aspergillus fumigatus biofilm formation. FEMS Microbiol Lett 313: 96–102.
Not in our library10.1111/j.1574-6968.2010.02130.x
192.
Müller, C.F., Seider, M., and Beauvais, A. (2011 ) Aspergillus fummigatus biofilms in a clinical setting. Med Mycol 49: 96–100.
Not in our library10.3109/13693786.2010.502190
193.
Nedel, W.L., and Pasqualotto, A.C. (2014 ) Treatment of infections by cryptic Aspergillus species. Mycopathologia 178: 441–445.
Not in our library10.1007/s11046-014-9811-z
194.
Negri, C.E., Gonçalves, S.S., Xafranski, H., Bergamasco, M.D., Aquino, V.R., Castro, P.T., et al (2014 ) Cryptic and rare Aspergillus species in Brazil: prevalence in clinical samples and in vitro susceptibility to triazoles. J Clin Microbiol 52: 3633–3640.
Not in our library10.1128/jcm.01582-14
195.
Nicholson, W.J., Slight, J., and Donaldson, K. (1996 ) Inhibition of the transcription factors NF‐kappa B and AP‐1 underlies loss of cytokine gene expression in rat alveolar macrophages treated with a diffusible product from the spores of Aspergillus fumigatus. Am J Resp Cell Mol 15: 88–96.
Not in our library10.1165/ajrcmb.15.1.8679226
196.
Nielsen, K., Marra, R.E., Hagen, F., Boekhout, T., Mitchell, T.G., Cox, G.M., et al (2005 ) Interaction between genetic background and the mating‐type locus in Cryptococcus neoformans virulence potential. Genetics 171: 975–983.
Not in our library10.1534/genetics.105.045039
197.
Nieminen, S.M., Karki, R., Auriola, S., Toivola, M., Laatsch, H., Laatikainen, R., et al (2002 ) Isolation and identification of Aspergillus fumigatus mycotoxins on growth medium and some building materials. Appl Environ Microbiol 68: 4871–4875.
Not in our library10.1128/aem.68.10.4871-4875.2002
198.
Nierman, W.C., Pain, A., Anderson, M.J., Wortman, J.R., Kim, H.S., Arroyo, J., et al (2005 ) Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438: 1151–1156.
Not in our library10.1038/nature04332
199.
Noni, M., Katelari, A., Dimopoulos, G., Doudounakis, S.E., Tzoumaka‐Bakoula, C., and Spoulou, V. (2015 ) Aspergillus fumigatus chronic colonization and lung function decline in cystic fibrosis may have a two‐way relationship. Eur J Clin Microbiol Infect Dis 34: 2235–2241.
Not in our library10.1007/s10096-015-2474-y
200.
Nosanchuk, J.D., and Casadevall, A. (2006 ) Impact of melanin on microbial virulence and clinical resistance to antimicrobial compounds. Antimicrob Agents Chemother 50: 3519–3528.
Not in our library10.1128/aac.00545-06
201.
Nucci, M., Nouér, S.A., Cappone, D., and Anaissie, E. (2013 ) Early diagnosis of invasive pulmonary aspergillosis in hematologic patients: an opportunity to improve the outcome. Haematological 98: 1657–1660.
Not in our library10.3324/haematol.2013.094359
202.
O'Gorman, C.M., Fuller, H., and Dyer, P.S. (2009 ) Discovery of a sexual cycle in the opportunistic fungal pathogen Aspergillus fumigatus. Nature 457: 471–474.
Not in our library10.1038/nature07528
203.
Ohba, H., Miwa, S., Shirai, M., Kanai, M., Eifuku, T., Suda, T., et al (2012 ) Clinical characteristics and prognosis of chronic pulmonary aspergillosis. Respir Med 106: 724–729.
Not in our library10.1016/j.rmed.2012.01.014
204.
Oliveira, M., and Caramalho, R. (2014 ) Aspergillus fumigatus: a mere bioaerosol or a powerful biohazard? NACC Bioloxia 21: 57–64.
Not in our library
205.
Oren, A., and Hallsworth, J.E. (2014 ) Microbial weeds in hypersaline habitats: the enigma of the weed‐like Haloferax mediterranei’. FEMS Microbiol Lett 359: 134–142.
Not in our library10.1111/1574-6968.12571
206.
Osherov, N. (2012 ) Interaction of the pathogenic mold Aspergillus fumigatus with lung epithelial cells. Front Microbiol 3: 346.
Not in our library10.3389/fmicb.2012.00346
207.
Ouedraogo, J.P., Hagen, S., Spielvogel, A., Engelhardt, S., and Meyer, V. (2011 ) Survival strategies of yeast and filamentous fungi against the antifungal protein AFP. J Biol Chem 286: 13859–13868.
Not in our library10.1074/jbc.m110.203588
208.
Pal, A.K., Gajjar, D.U., and Vasavada, A.R. (2014 ) DOPA and DHN pathway orchestrate melanin synthesis in Aspergillus species. ISHAM 52: 10–18.
Not in our library10.3109/13693786.2013.826879
209.
Paoletti, M., Rydholm, C., Schwier, E.U., Anderson, M.J., Szakacs, G., Lutzoni, F., et al (2005 ) Evidence for sexuality in the opportunistic fungal pathogen Aspergillus fumigatus. Curr Biol 15: 1242–1248.
Not in our library10.1016/j.cub.2005.05.045
210.
Papagianni, M., Avramidis, N., and Filiousis, G. (2007 ) Glycolysis and regulation of glucose transport in Lactococcus lactis spp. lactis in batch and fed‐batch culture. Microb Cell Fact 6: 16–29.
Not in our library10.1186/1475-2859-6-16
211.
Paris, S., Wysong, D., Debeaupuis, J.P., Shibuya, K., Philippe, B., Diamond, R.D., et al (2003 ) Catalases of Aspergillus fumigatus. Infect Immun 71: 3551–3562.
Not in our library10.1128/iai.71.6.3551-3562.2003
212.
Paulussen, C., Boulet, G.A., Cos, P., Delputte, P., and Maes, L.J. (2014 ) Animal models of invasive aspergillosis for drug discovery. Drug Discov Today 19: 1380–1386.
Not in our library10.1016/j.drudis.2014.06.006
213.
Pedrini, N., Ortiz‐Urquiza, A., Huarte‐Bonnet, C., Fan, Y., Juárez, M.P., and Keyhani, N.O. (2015 ) Tenebrionid secretions and a fungal benzoquinone oxidoreductase form competing components of an arms race between a host and pathogen. Proc Natl Acad Sci USA 112: E3651–E3660.
Not in our library10.1073/pnas.1504552112
214.
Perfect, J.R., Cox, G.M., Lee, J.Y., Kauffman, C.A., de Repentigny, L., Chapman, S.W., et al (2001 ) The impact of culture isolation of Aspergillus species: a hospital‐based survey of aspergillosis. Clin Infect Dis 33: 1824–1833.
Not in our library10.1086/323900
215.
Perlin, D.S., Shor, E., and Zhao, Y. (2015 ) Update on antifungal drug resistance. Curr Clin Microbiol Rep 2: 84–95.
Not in our library10.1007/s40588-015-0015-1
216.
Perrone, G., Stea, G., Epifani, F., Varga, J., Frisvad, J.C., and Samson, R.A. (2011 ) Aspergillus niger contains the cryptic phylogenetic species A. awamori. Fungal Biol 115: 1138–1150.
Not in our library10.1016/j.funbio.2011.07.008
217.
Persons, D.D., Hess, G.D., Muller, W.J., and Scherer, P.W. (1987 ) Airway deposition of hyroscopic heterodispersed aerosols: results of a computer calculation. J Appl Physiol 63: 1195–1204.
Not in our library10.1152/jappl.1987.63.3.1195
218.
Petelenz‐Kurdziel, E., Kuehn, C., Nordlander, B., Klein, D., Hong, K., Joacobson, T., et al (2013 ) Quantitive analysis of glycerol accumulation, glycolysis and growth under hyper osmotic stress. PLoS Comput Biol 9: e1003084.
Not in our library10.1371/journal.pcbi.1003084
219.
Picard, D. (2002 ) Heat‐shock protein 90, a chaperone for folding and regulation. Cell Mol Life Sci 59: 1640–1648.
Not in our library10.1007/pl00012491
220.
Pochon, S., Simoneau, P., Pigne, S., Balides, S., Bataillé‐Simoneau, N., Campion, C., et al (2013 ) Dehydrin‐ like proteins in the necrotrophic fungus Alternaria brassicicola have a role in plant pathogenesis and stress response. PLoS ONE 8: e75143.
Not in our library10.1371/journal.pone.0075143
221.
Pohl, C.H., Kock, J.L.F. and Thibane, V.S. (2011 ) Antifungal free fatty acids: a review In Science against Microbial Pathogens: Communicating Current Research and Technological Advances. Méndez‐Vilas A. (ed) Spain: Formatex Research Center, 1: 61–71.
Not in our library
222.
Pontecorvo, G., Roper, J.A., and Forbes, E. (1953 ) Genetic recombination without sexual reproduction in Aspergillus niger. J Gen Microbiol 8: 198–210.
Not in our library10.1099/00221287-8-1-198
223.
Rahardjo, Y.S.P., Weber, F.J., Haemers, S., Tramper, J., and Rinzema, A. (2005a ) Aerial mycelia of Aspergillus oryzae accelerate α‐amylase production in a model solid‐state fermentation system. Enzyme Microb Technol 36: 900–902.
Not in our library
224.
Rahardjo, Y.S.P., Sie, S., Weber, F.J., Tramper, J., and Rinzema, A. (2005b ) Effect of low oxygen concentrations on growth and α‐amylase production of Aspergillus oryzae in model solid‐state fermentation systems. Biomol Eng 21: 163–172.
Not in our library10.1016/j.bioeng.2005.01.001
225.
Ramage, G., Rajendran, R., Gutierrez‐Correa, M., Jones, B., and Williams, C. (2011 ) Aspergillus biofilms: clinical and industrial significance. FEMS Microbiol Lett 324: 89–97.
Not in our library10.1111/j.1574-6968.2011.02381.x
226.
Rangel, D.E., Braga, G.U., Fernandes, É.K., Keyser, C.A., Hallsworth, J.E., and Roberts, D.W. (2015a ) Stress tolerance and virulence of insect‐pathogenic fungi are determined by environmental conditions during conidial formation. Curr Genet 61: 383–404.
Not in our library10.1007/s00294-015-0477-y
227.
Rangel, D.E.N., Alder‐Rangel, A., Dadachova, E., Finlay, R.D., Kupiec, M., Dijksterhuis, J., et al (2015b ) Fungal stress biology: a preface to the Fungal Stress Responses special edition. Curr Genet 61: 231–238.
Not in our library10.1007/s00294-015-0500-3
228.
Ranjendran, R., Mowat, E., McClloch, E., Lappin, D.F., Jones, B., Lang, S., et al (2011 ) Azole resistance of Aspergillus fumigatus biofilms is partly associated with efflux pump activity. Antimicrob Agents Chemother 55: 2092–2097.
Not in our library10.1128/aac.01189-10
229.
Redkar, R.J., Herzog, R.W., and Singh, N.K. (1998 ) Transcriptional activation of the Aspergillus nidulans gpdA promoter by osmotic signals. Appl Environ Microbiol 64: 2229–2231.
Not in our library10.1128/aem.64.6.2229-2231.1998
230.
Double-stranded RNA mycovirus infection of Aspergillus fumigatus is not dependent on the genetic make-up of the host. · 2013
Not checked
231.
Richardson, M.D. and Hope, W. (2003 ) Aspergillus In Clinical Mycology. Anaissie E.J., McGinnis M.R. and Pfaller M.A. (eds). New York: Churchill Livingstone xii, pp. 608.
Not in our library
232.
Roilides, E., and Simitsopoulou, M. (2011 ) Local innate host response and filamentous fungi in patients with cystic fibrosis. Med Mycol 48: S22–S31.
Not in our library10.3109/13693786.2010.511286
233.
Ruijter, G.J.G., Bax, M., Patel, H., Flitter, S.J., van Kuyk, P.A., and Visser, J. (2003 ) Mannitol is required for stress tolerance in Aspergillus niger conidiospores. Eukaryot Cell 2: 690–698.
Not in our library10.1128/ec.2.4.690-698.2003
234.
Rummel, J.D., Beaty, D.W., Jones, M.A., Bakermans, C., Barlow, N.G., Boston, P., et al (2014 ) A new analysis of Mars ‘Special Regions’, findings of the second MEPAG Special Regions Science Analysis Group (SR‐SAG2). Astrobiology 14: 887–968.
Not in our library10.1089/ast.2014.1227
235.
Ryckeboer, J., Mergaert, J., Coosemans, J., Deprins, K., and Swings, J. (2003 ) Microbiological aspects of biowaste during composting in a monitored compost bin. J Appl Microbiol 94: 127–137.
Not in our library10.1046/j.1365-2672.2003.01800.x
236.
Saleem, A., and Ebrahim, M.K.H. (2014 ) Production of amylase by fungi isolated from legume seeds collected in Almandinah Almunawwarah, Saudi Arabia. J Taibah Univ Sci 8: 90–97.
Not in our library
237.
Sales‐Campos, H., Tonani, L., Ribeiro, C., Cardosis, B., and Von Zeska Kress, M.R. (2013 ) The immune interplay between the host and the pathogen Aspergillus fumigatus lung infection. Biomed Res Int 2013: 693023.
Not in our library10.1155/2013/693023
238.
Samson, R.A., Varga, J., Witiak, S.M., and Geiser, D.M. (2007 ) The species concept in Aspergillus: recommendations of an international panel. Stud Mycol 59: 71–73.
Not in our library10.3114/sim.2007.59.09
239.
Samson, R.A., Visagie, C.M., Houbraken, J., Hong, S.B., Hubka, V., Klaassen, C.H., et al (2014 ) Phylogeny, identification and nomenclature of the genus Aspergillus. Stud Mycol 78: 141–173.
Not in our library10.1016/j.simyco.2014.07.004
240.
Santos, R., Stevenson, A., de Carvalho, C.C.C.R., Grant, I.R., and Hallsworth, J.E. (2015 ) Extraordinary solute stress tolerance contributes to the environmental tenacity of mycobacteria. Environ Microbiol Rep 7: 746–764.
Not in our library10.1111/1758-2229.12306
241.
Scharf, D.H., Heinekamp, T., Remme, N., Hortschansky, P., Brakhage, A.A., and Hertweck, C. (2012 ) Biosynthesis and function of gliotoxin in Aspergillus fumigatus. Appl Microbiol Biotech 93: 467–472.
Not in our library10.1007/s00253-011-3689-1
242.
Schindler, A.F., Palmer, J.G., and Eisenberg, W.V. (1967 ) Aflotoxin production by Aspergillus flavus as related to various temperatures. Appl Microbiol 15: 1006–1009.
Not in our library10.1128/am.15.5.1006-1009.1967
243.
Schmaler‐Ripcke, J., Sugareva, V., Gebhardt, P., Winkler, R., Kniemeyer, O., Heinekamp, T., et al (2009 ) Production of pyomelanin, a second type of melanin, via the tyrosine degradation pathway in Aspergillus fumigatus. Appl Environ Microbiol 75: 493–503.
Not in our library10.1128/aem.02077-08
244.
Schmit, J.C., and Brody, S. (1976 ) Biochemical genetics of Neurosporia crassa conidial germination. Bacteriol Rev 40: 1–41.
Not in our library10.1128/br.40.1.1-41.1976
245.
Schoch, C.L., Seifert, K.A., Huhndorf, S., Robert, V., Spouge, J.L., Levesque, C.A., et al (2012 ) Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proc Natl Acad Sci USA 109: 6241–6246.
Not in our library10.1073/pnas.1117018109
246.
Schweer, K.E., Bangard, C., Hekmat, K., and Cornely, O.A. (2014 ) Chronic pulmonary aspergillosis. Mycoses 57: 257–270.
Not in our library10.1111/myc.12152
247.
Segal, B.H. (2009 ) Aspergillosis. N Engl J Med 360: 1870–1884.
Not in our library10.1056/nejmra0808853
248.
Seidler, M.J., Salvenmoser, S., and Müller, F.M.C. (2008 ) Aspergillus fumigatus forms biofilms with reduced antifungal drug susceptibility on bronchial epithelial cells. Antimicrob Agents Chemother 52: 4130–4136.
Not in our library10.1128/aac.00234-08
249.
Seyedmousavi, S., Mouton, J.W., Melchers, W.J., Brüggemann, R.J., and Verweij, P.E. (2014 ) The role of azoles in the management of azole‐resistant aspergillosis: from the bench to the bedside. Drug Resist Update 17: 37–50.
Not in our library10.1016/j.drup.2014.06.001
250.
Sharma, D.C. (2005 ) Asthma in young children. Environ Health Perspect 113: 836–838.
Not in our library
251.
Sharma, R., Singh Kocher, G., Singh Bhogal, R., and Singh Oberoi, H. (2014 ) Cellulolytic and xylanolytic enzymes from thermophilic Aspergillus terreus RWY. J Basic Microbiol 54: 1367–1377.
Not in our library10.1002/jobm.201400187
252.
Sharova, E.I. (2007 ) Expansins: proteins involved in cell wall softening during plant growth and morphgenesis. Russ J Plant Physiol 54: 713–727.
Not in our library
253.
Adaptive melanin response of the soil fungus Aspergillus niger to UV radiation stress at "Evolution Canyon", Mount Carmel, Israel. · 2008
Not checked
254.
Singh, N.M., Husain, S., and AST Infectious Diseases Community of Practice (2013 ) Aspergillosis in solid organ transplantation. Am J Transplant 13: 228–241.
Not in our library10.1111/ajt.12115
255.
Singh, N., and Paterson, D.L. (2005 ) Aspergillus infections in transplant recipients. Clin Microbiol Rev 18: 44–69.
Not in our library10.1128/cmr.18.1.44-69.2005
256.
Skov, M., Pressler, T., Jensen, H.E., Høiby, N., and Koch, C. (1999 ) Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA). Thorax 54: 44–50.
Not in our library10.1136/thx.54.1.44
257.
Skromme, I., Sánchez, O., and Aguirre, J. (1995 ) Starvation stess modulates the expression of the Aspergillus nidulans brlA regulatory gene. Microbiology 141: 21–28.
Not in our library10.1099/00221287-141-1-21
258.
Slavin, R.G., Bedrossian, C.W., Hutcheson, P.S., Pittman, S., Salinas‐Madrigal, L., Tsai, C.C., et al (1988 ) A pathologic study of allergic bronchopulmonary aspergillosis. J Allergy Clin Immunol 81: 718–725.
Not in our library10.1016/0091-6749(88)91044-5
259.
Slesiona, S., Gressler, M., Mihlan, M., Zaehle, C., Schaller, M., Barz, D., et al (2012 ) Persistence versus escape: Aspergillus terreus and Aspergillus fumigatus employ different strategies during interactions with macrophages. PLoS ONE 7: e31223.
Not in our library10.1371/journal.pone.0031223
260.
Smith, K., Rajendran, R., Kerr, S., Lappin, D.F., Mackay, W.G., Williams, C., et al (2015 ) Aspergillus fumigatus enhances elastase production in Pseudomonas aeruginosa co‐cultures. Med Mycol 53: 645–655.
Not in our library10.1093/mmy/myv048
261.
Steif, P., Fuchs‐Ocklenburg, S., Kamp, A., Manchar, C., Houbraken, J., Boekhout, T., et al (2014 ) Dissimilatory nitrate reduction by Aspergillus terreus isolated from the seasonal oxygen minimum zone in the Arabian Sea. BMC Microbiol 14: 1–10.
Not in our library10.1186/1471-2180-14-35
262.
Steinbach, W.J. (2008 ) Clinical aspects of the genus Aspergillus In The Aspergilli: Genomics, Medical Aspects, Biotechnology and Research Methods. Goldman G.H. and Osmani S.A. (ed). Boca Raton, FL: Taylor & Francis Group, LLC, pp. 537.
Not in our library
263.
Stevenson, A., and Hallsworth, J.E. (2014 ) Water and temperature relations of soil Actinobacteria. Environ Microbiol Rep 6: 744–755.
Not in our library10.1111/1758-2229.12199
264.
Is there a common water-activity limit for the three domains of life? · 2014
No notice
265.
Stevenson, A., Burkhardt, J., Cockell, C.S., Cray, J.A., Dijksterhuis, J., Fox‐Powell, M., et al (2015b ) Multiplication of microbes below 0.690 water activity: implications for terrestrial and extraterrestrial life. Environ Microbiol 17: 257–277.
Not in our library10.1111/1462-2920.12598
266.
Sugui, J.A., Pardo, J., Chang, Y.C., Zarember, K.A., Nardone, G., Galvez, E.M., et al (2007 ) Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisone. Eukaryot Cell 6: 1562–1569.
Not in our library10.1128/ec.00141-07
267.
Sugui, J.A., Vinh, D.C., Nardone, G., Shea, Y.R., Chang, Y.C., Zelazny, A.M., et al (2010 ) Neosartorya udagawae (Aspergillus udagawae), an emerging agent of aspergillosis: how different is it from Aspergillus fumigatus? J Clin Microbiol 48: 220–228.
Not in our library10.1128/jcm.01556-09
268.
Sugui, J.A., Losada, L., Wang, W., Varga, J., Ngamskulrungroj, P., Abu‐Asab, M., et al (2011 ) Identification and characterization of an Aspergillus fumigatus “Supermater” pair. mBio 2: e00234–00211.
Not in our library10.1128/mbio.00234-11
269.
Sugui, J.A., Peterson, S.W., Figat, A., Hansen, B., Samson, R.A., Mellado, E., et al (2014 ) Genetic relatedness versus biological compatibility between Aspergillus fumigatus and related species. J Clin Microbiol 52: 3707–3721.
Not in our library10.1128/jcm.01704-14
270.
Suryawanshi, R.K., Patil, C.D., Borase, H.P., Narkhede, C.P., Stevenson, A., Hallsworth, J.E., et al (2015 ) Towards an understanding of bacterial metabolites prodigiosin and violacein and their potential for use in commercial sunscreens. Int J Cosmetic Sci 37: 98–107.
Not in our library10.1111/ics.12175
271.
Sweeney, M.J., and Dobson, A.D.W. (1998 ) Review: mycotoxin production by Aspergillus, Fusarium and Penicillium species. Int J Food Microbiol 43: 141–158.
Not in our library10.1016/s0168-1605(98)00112-3
272.
Swilaiman, S.S., O'Gorman, C.M., Balajee, S.A., and Dyer, P.S. (2013 ) Discovery of a sexual cycle in Aspergillus lentulus, a close relative of A. fumigatus. Eukaryot Cell 12: 962–969.
Not in our library10.1128/ec.00040-13
273.
Taha, M.P.M., Pollard, S.J.T., Sarkar, U., and Longhurst, P. (2005 ) Estimating fugitive bioaerosol releases from static compost windrows: Feasibility of a portable wind tunnel approach. Waste Manage 25: 445–450.
Not in our library10.1016/j.wasman.2005.02.013
274.
Tekaia, F., and Latgé, J.P. (2005 ) Aspergillus fumigatus: saprophyte or pathogen? Curr Opin Microbiol 8: 385–392.
Not in our library10.1016/j.mib.2005.06.017
275.
Trehalose and Trehalose-based Polymers for Environmentally Benign, Biocompatible and Bioactive Materials · 2008
Not checked
276.
Thornton, C.R. (2010 ) Detection of invasive aspergillosis. Adv Appl Microbiol 70: 187–216.
Not in our library10.1016/s0065-2164(10)70006-x
277.
Thywißen, A., Heinekamp, T., Dahse, H.M., Schmaler‐Ripcke, J., Nietzsche, S., Zipfel, P.F., et al (2011 ) Conidial dihydroxynaphthalene melanin of the human pathogenic fungus Aspergillus fumigatus interferes with the host endocytosis pathway. Front Microbiol 2: 96. doi:10.3389/fmicb.2011.00096.
Not in our library10.3389/fmicb.2011.00096
278.
Tomee, J.F., and Kauffman, H.F. (2000 ) Putative virulence factors of Aspergilllus fumigatus. Clin Exp Allergy 30: 476–484.
Not in our library10.1046/j.1365-2222.2000.00796.x
279.
Upadhyay, S., Torres, G., and Lin, X. (2013 ) Laccases involved in 1,8‐dihydroxynaphthalene melanin biosynthesis in Aspergillus fumigatus are regulated by developmental factors and copper homeostasis. Eukaryot Cell 12: 1641–1652.
Not in our library10.1128/ec.00217-13
280.
The Aspergillus fumigatus cell wall integrity signaling pathway: drug target, compensatory pathways, and virulence · 2015
No notice
281.
Valsecchi, I., Mellado, E., Beau, R., and Latgé, J.P. (2015 ) Fitness studies of azole‐resistant strains of Aspergillus fumigatus. Antimicrob Agents Chemother 59: 7866–7869.
Not in our library10.1128/aac.01594-15
282.
Antifungal Resistance and New Strategies to Control Fungal Infections · 2012
No notice
283.
Varga, J., Houbraken, J., Van Der Lee, H.A., Verweij, P.E., and Samson, R.A. (2008 ) Aspergillus calidoustus sp. nov., causative agent of human infections previously assigned to Aspergillus ustus. Eukaryot Cell 7: 630–638.
Not in our library10.1128/ec.00425-07
284.
Varga, J., Szigeti, G., Baranyi, N., Kocsube, S., O'Gorman, C.M., and Dyer, P.S. (2014 ) Aspergillus: sex and recombination. Mycopathologia 178: 349–362.
Not in our library10.1007/s11046-014-9795-8
285.
Venkatesh, M.V., Joshi, K.R., Harjai, S.C., and Ramdeo, I.N. (1975 ) Aspergillosis in desert locust (Schistocerca‐gregaria forsk). Mycopathologia 57: 135–138.
Not in our library10.1007/bf00551419
286.
Vermeulen, E., Maertens, J., De Bel, A., Nulens, E., Boelens, J., Surmont, I., et al (2015 ) Nationwide surveillance of azole resistance in Aspergillus diseases. Antimicrob Agents Chemother 59: 4569–4576.
Not in our library10.1128/aac.00233-15
287.
Villena, G.K., and Gutiérrez‐Correa, M. (2007 ) Production of lignocellulolytic enzymes by Aspergillus niger biofilms at variable water activities. Electron J Biotechnol 10: 124–140.
Not in our library
288.
Walley, J.W., Kliebenstein, D.J., Bostock, R.M., and Dehesh, K. (2013 ) Fatty acids and early detection of pathogens. Curr Opin Plant Biol 16: 520–526.
Not in our library10.1016/j.pbi.2013.06.011
289.
Wasylnka, J.A., Simmer, M.I., and Moore, M.M. (2001 ) Differences in sialic acid density in pathogenic and non‐pathogenic Aspergillus species. Microbiology 147: 869–877.
Not in our library10.1099/00221287-147-4-869
290.
Whittaker Leclair, L., and Hogan, D.A. (2010 ) Mixed bacterial‐fungal infections in the CF respiratory tract. Med Mycol 48: S125–S132.
Not in our library10.3109/13693786.2010.521522
291.
Williams, J.P., and Hallsworth, J.E. (2009 ) Limits of life in hostile environments: no barriers to biosphere function? Environ Microbiol 11: 3292–3308.
Not in our library10.1111/j.1462-2920.2009.02079.x
292.
Winkelströter, L.K., Dolan, S.K., dos Reis, T.F., Bom, V.L.P., de Alves Castro, P., Hagiwara, D., et al (2015 ) Systematic global analysis of genes encoding protein phosphatases in Aspergillus fumigatus. G3: Genes ‐ Genomes ‐ Genetics 5: 1525–1539.
Not in our library10.1534/g3.115.016766
293.
Biodiversity and biogeography of the atmosphere · 2010
No notice
294.
Womack, A.M., Artaxo, P.E., Ishida, F.Y., Mueller, R.C., Saleska, S.R., Wiedemann, K.T., et al (2015 ) Characterization of active and total fungal communities in the atmosphere over the Amazon rainforest. Biogeosci 12: 6337–6349.
Not in our library
295.
Wong Sak Hoi, J., Beau, R. and Latgé, J. (2012 ) A novel dehydrin‐like protein from Aspergillus fumigatus regulates freezing tolerance. Fungal Genet Biol 49: 210–216.
Not in our library10.1016/j.fgb.2012.01.005
296.
Wyatt, T.T., Wösten, H.A.B., and Dijksterhuis, J. (2013 ) Fungal spores for dispersion in time and space. Adv Appl Microbiol 85: 43–91.
Not in our library10.1016/b978-0-12-407672-3.00002-2
297.
Wyatt, T.T., Golovina, E.A., Leeuwen, R., Hallsworth, J.E., Wösten, H.A., and Dijksterhuis, J. (2015a ) A decrease in bulk water and mannitol and accumulation of trehalose and trehalose‐based oligosaccharides define a two‐stage maturation process towards extreme stress resistance in ascospores of Neosartorya fischeri (Aspergillus fischeri). Environ Microbiol 17: 383–394.
Not in our library10.1111/1462-2920.12557
298.
Wyatt, T.T., van Leeuwen, M.R., Golovina, E.A., Hoekstra, F.A., Kuenstner, E.J., Palumbo, E.A., et al (2015b ) Functionality and prevalence of trehalose‐based oligosaccharides as novel compatible solutes in ascospores of Neosartorya fischeri (Aspergillus fischeri) and other fungi. Environ Microbiol 17: 395–411.
Not in our library10.1111/1462-2920.12558
299.
Yakimov, M.M., Lo Cono, V., La Spada, G., Bortoluzzi, G., Messina, E., Smedile, F., et al (2015 ) Microbial community of seawater‐brine interface of the deep‐sea brine Lake Kryos as revealed by recovery of mRNA are active below the chaotropicity limit of life. Environ Microbiol 17: 364–382.
Not in our library10.1111/1462-2920.12587
300.
Young, P.L., and Saxena, M. (2014 ) Fever management in intensive care patients with infections. Crit Care 18: 206–215.
Not in our library10.1186/cc13773
301.
Yu, J.H. (2010 ) Regulation of development in Aspergillus nidulans and Aspergillus fumigatus. Mycobiology 38: 229–237.
Not in our library10.4489/myco.2010.38.4.229
302.
Zhang, Z., Liu, R., Noordhoek, J.A., and Kauffman, H.F. (2005 ) Interaction of airway epithelial cells (A549) with spores and mycelium of Aspergillus fumigatus. J Infect 51: 375–382.
Not in our library10.1016/j.jinf.2004.12.012
303.
Zhang, J., Debets, A.J.M., Verweij, P.E., Melchers, W.J.G., Zwann, B.J., and Schoustra, S.E. (2015 ) Asexual sporulation facilitates adaptation: The emergence of azole resistance in Aspergillus fumigatus. Evolution 69: 2573–2586.
Not in our library10.1111/evo.12763
304.
Zhao, W., Li, C., Liang, J., and Sun, S. (2014 ) The Aspergillus fumigatus β‐1,3‐glucanosytransferase Gel7 plays a compensatory role in maintaining cell wall integrity under stress conditions. Glycobiology 24: 418–427.
Not in our library10.1093/glycob/cwu003
305.
Zucchi, T.D., Zucchi, F.D., Poli, P., Melo, I.S., and Zucchi, T.M.A.D. (2005 ) A short‐term test adapted to detect the genotoxic effects of environmental volatile pollutants (benzene fumes) using the filamentous fungus Aspergillus nidulans. J Environ Monit 7: 598–602.
Not in our library10.1039/b500219b

Cited by papers we hold 5

Reads

Read by people on this page

None yet.

Checked or read by AI through naulon

None yet.

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.

Are you an author?

Is this your paper?

Claim it to add your note and be paid when agents cite it. Free.