Carbon source‐induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen C andida albicans

Abstract

The major fungal pathogen C andida albicans can occupy diverse microenvironments in its human host. During colonization of the gastrointestinal or urogenital tracts, mucosal surfaces, bloodstream, and internal organs, C . albicans thrives in niches that differ with respect to available nutrients and local environmental stresses. Although most studies are performed on glucose‐grown cells, changes in carbon source dramatically affect cell wall architecture, stress responses, and drug resistance. We show that growth on the physiologically relevant carboxylic acid, lactate, has a significant impact on the C . albicans cell wall proteome and secretome. The regulation of cell wall structural proteins (e.g. C ht1, P hr1, P hr2, P ir1) correlated with extensive cell wall remodeling in lactate‐grown cells and with their increased resistance to stresses and antifungal drugs, compared with glucose‐grown cells. Moreover, changes in other proteins (e.g. A ls2, G ca1, P hr1, S ap9) correlated with the increased adherence and biofilm formation of lactate‐grown cells. We identified mating and pheromone‐regulated proteins that were exclusive to lactate‐grown cells (e.g. O p4, P ga31, P ry1, S cw4, Y ps7) as well as mucosa‐specific and other niche‐specific factors such as L ip4, P ga4, P lb5, and S ap7. The analysis of the corresponding null mutants confirmed that many of these proteins contribute to C . albicans adherence, stress, and antifungal drug resistance. Therefore, the cell wall proteome and secretome display considerable plasticity in response to carbon source. This plasticity influences important fitness and virulence attributes known to modulate the behavior of C . albicans in different host microenvironments during infection.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 85

1. 1.

   Calderone RA, Clancy CJ. Candida and Candidiasis. 2011.

   Not in our library

2. 2.

   Calderone RA, Fonzi WA. Virulence factors of Candida albicans. Trends Microbiol. 2001;9:327-335.

   Not in our library10.1016/s0966-842x(01)02094-7

3. 3.

   Murad AM, d'Enfert C, Gaillardin C, Tournu H, et al. Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1. Mol. Microbiol. 2001;42:981-993.

   Not in our library10.1046/j.1365-2958.2001.02713.x

4. 4.

   Nantel A, Dignard D, Bachewich C, Harcus D, et al. Transcription profiling of Candida albicans cells undergoing the yeast-to-hyphal transition. Mol. Biol. Cell. 2002;13:3452-3465.

   Not in our library10.1091/mbc.e02-05-0272

5. 5.

   Lorenz MC, Fink GR. The glyoxylate cycle is required for fungal virulence. Nature. 2001;412:83-86.

   Not in our library10.1038/35083594

6. 6.

   Fradin C, Hube B. Tissue infection and site-specific gene expression in Candida albicans. Adv. Appl. Microbiol. 2003;53:271-290.

   Not in our library10.1016/s0065-2164(03)53008-8

7. 7.

   Fradin C, De Groot P, MacCallum D, Schaller M, et al. Granulocytes govern the transcriptional response, morphology and proliferation of Candida albicans in human blood. Mol. Microbiol. 2005;56:397-415.

   Not in our library10.1111/j.1365-2958.2005.04557.x

8. 8.

   Rubin-Bejerano I, Fraser I, Grisafi P, Fink GR. Phagocytosis by neutrophils induces an amino acid deprivation response in Saccharomyces cerevisiae and Candida albicans. Proc. Natl. Acad. Sci. USA. 2003;100:11007-11012.

   Not in our library10.1073/pnas.1834481100

9. 9.

   Barelle CJ, Priest CL, Maccallum DM, Gow NA, et al. Niche-specific regulation of central metabolic pathways in a fungal pathogen. Cell. Microbiol. 2006;8:961-971.

   Not in our library10.1111/j.1462-5822.2005.00676.x

10. 10.

    Thewes S, Kretschmar M, Park H, Schaller M, et al. In vivo and ex vivo comparative transcriptional profiling of invasive and non-invasive Candida albicans isolates identifies genes associated with tissue invasion. Mol. Microbiol. 2007;63:1606-1628.

    Not in our library10.1111/j.1365-2958.2007.05614.x

11. 11.

    Brown AJ, Odds FC, Gow NA. Infection-related gene expression in Candida albicans. Curr. Opin. Microbiol. 2007;10:307-313.

    Not in our library10.1016/j.mib.2007.04.001

12. 12.

    Price MS, Betancourt-Quiroz M, Price JL, Toffaletti DL, et al. Cryptococcus neoformans requires a functional glycolytic pathway for disease but not persistence in the host. MBio. 2011;2:e00103-11.

    Not in our library10.1128/mbio.00103-11

13. 13.
    The Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content> Autoinduces Hyphal Morphogenesis by Raising Extracellular pH · 2011

    Not checked
14. 14.

    Khatib R, Riederer KM, Ramanathan J, Baran J. Faecal fungal flora in healthy volunteers and inpatients. Mycoses. 2001;44:151-156.

    Not in our library10.1046/j.1439-0507.2001.00639.x

15. 15.
    In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide · 2011

    No notice
16. 16.

    Buchalter SE, Crain MR, Kreisberg R. Regulation of lactate metabolism in vivo. Diabetes Metab. Rev. 1989;5:379-391.

    Not in our library10.1002/dmr.5610050405

17. 17.

    Ueno K, Matsumoto Y, Uno J, Sasamoto K, et al. Intestinal resident yeast Candida glabrata requires Cyb2p-mediated lactate assimilation to adapt in mouse intestine. PLoS One. 2011;6:e24759.

    Not in our library10.1371/journal.pone.0024759

18. 18.

    Lorenz MC, Bender JA, Fink GR. Transcriptional response of Candida albicans upon internalization by macrophages. Eukaryot. Cell. 2004;3:1076-1087.

    Not in our library10.1128/ec.3.5.1076-1087.2004

19. 19.

    Ramirez MA, Lorenz MC. The transcription factor homolog CTF1 regulates {beta}-oxidation in Candida albicans. Eukaryot. Cell. 2009;8:1604-1614.

    Not in our library10.1128/ec.00206-09

20. 20.

    Klis FM, de Groot P, Hellingwerf K. Molecular organization of the cell wall of Candida albicans. Med. Mycol. 2001;39(Suppl 1):1-8.

    Not in our library

21. 21.

    Ruiz-Herrera J, Elorza MV, Valentin E, Sentandreu R. Molecular organization of the cell wall of Candida albicans and its relation to pathogenicity. FEMS Yeast Res. 2006;6:14-29.

    Not in our library10.1111/j.1567-1364.2005.00017.x

22. 22.

    Klis FM, Sosinska GJ, de Groot PW, Brul S. Covalently linked cell wall proteins of Candida albicans and their role in fitness and virulence. FEMS Yeast Res. 2009;9:1013-1028.

    Not in our library10.1111/j.1567-1364.2009.00541.x

23. 23.

    Schaller M, Borelli C, Korting HC, Hube B. Hydrolytic enzymes as virulence factors of Candida albicans. Mycoses. 2005;48:365-377.

    Not in our library10.1111/j.1439-0507.2005.01165.x

24. 24.

    Calderone RA, Braun PC. Adherence and receptor relationships of Candida albicans. Microbiol. Rev. 1991;55:1-20.

    Not in our library10.1128/mr.55.1.1-20.1991

25. 25.

    Sundstrom P. Adhesion in Candida spp. Cell. Microbiol. 2002;4:461-469.

    Not in our library10.1046/j.1462-5822.2002.00206.x

26. 26.

    Lipke PN, Garcia MC, Alsteens D, Ramsook CB, et al. Strengthening relationships: amyloids create adhesion nanodomains in yeasts. Trends Microbiol. 2012;20:59-65.

    Not in our library10.1016/j.tim.2011.10.002

27. 27.

    Lowman DW, Ensley HE, Greene RR, Knagge KJ, et al. Mannan structural complexity is decreased when Candida albicans is cultivated in blood or serum at physiological temperature. Carbohydr. Res. 2011;346:2752-2759.

    Not in our library10.1016/j.carres.2011.09.029

28. 28.
    Host carbon sources modulate cell wall architecture, drug resistance and virulence in a fungal pathogen · 2012

    No notice
29. 29.

    Kapteyn JC, Hoyer LL, Hecht JE, Muller WH, et al. The cell wall architecture of Candida albicans wild-type cells and cell wall-defective mutants. Mol. Microbiol. 2000;35:601-611.

    Not in our library10.1046/j.1365-2958.2000.01729.x

30. 30.

    Verstrepen KJ, Klis FM. Flocculation, adhesion and biofilm formation in yeasts. Mol. Microbiol. 2006;60:5-15.

    Not in our library10.1111/j.1365-2958.2006.05072.x

31. 31.

    Sorgo AG, Heilmann CJ, Dekker HL, Brul S, et al. Mass spectrometric analysis of the secretome of Candida albicans. Yeast. 2010;27:661-672.

    Not in our library10.1002/yea.1775

32. 32.

    Sorgo AG, Heilmann CJ, Dekker HL, Bekker M, et al. Effects of fluconazole on the secretome, the wall proteome, and wall integrity of the clinical fungus Candida albicans. Eukaryot. Cell. 2011;10:1071-1081.

    Not in our library10.1128/ec.05011-11

33. 33.

    Murad AM, Lee PR, Broadbent ID, Barelle CJ, Brown AJ. CIp10, an efficient and convenient integrating vector for Candida albicans. Yeast. 2000;16:325-327.

    Not in our library10.1002/1097-0061(20000315)16:4<325::aid-yea538>3.0.co;2-#

34. 34.

    Dennison PM, Ramsdale M, Manson CL, Brown AJ. Gene disruption in Candida albicans using a synthetic, codon-optimised Cre-loxP system. Fungal Genet. Biol. 2005;42:737-748.

    Not in our library10.1016/j.fgb.2005.05.006

35. 35.

    Netea MG, Gow NA, Munro CA, Bates S, et al. Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J. Clin. Invest. 2006;116:1642-1650.

    Not in our library10.1172/jci27114

36. 36.

    Heilmann CJ, Sorgo AG, Siliakus AR, Dekker HL, et al. Hyphal induction in the human fungal pathogen Candida albicans reveals a characteristic wall protein profile. Microbiology. 2011;157:2297-2307.

    Not in our library10.1099/mic.0.049395-0

37. 37.

    Yin QY, de Groot PW, Dekker HL, de Jong L, et al. Comprehensive proteomic analysis of Saccharomyces cerevisiae cell walls: identification of proteins covalently attached via glycosylphosphatidylinositol remnants or mild alkali-sensitive linkages. J. Biol. Chem. 2005;280:20894-20901.

    Not in our library10.1074/jbc.m500334200

38. 38.

    Backhaus K, Heilmann CJ, Sorgo AG, Purschke G, et al. A systematic study of the cell wall composition of Kluyveromyces lactis. Yeast. 2010;2:647-660.

    Not in our library10.1002/yea.1781

39. 39.

    Desjardins P, Hansen JB, Allen M. Microvolume spectrophotometric and fluorometric determination of protein concentration. Curr. Protoc. Protein Sci. 2009;3.

    Not in our library10.1002/0471140864.ps0310s55

40. 40.

    Bendtsen JD, Nielsen H, von Heijne G, Brunak S. Improved prediction of signal peptides: signalp 3.0. J. Mol. Biol. 2004;340:783-795.

    Not in our library10.1016/j.jmb.2004.05.028

Cited by papers we hold 5

• Carboxylic Acid Transporters in <italic toggle="yes">Candida</italic> Pathogenesis · 2020
  Not checked
• Adapting to survive: How Candida overcomes host-imposed constraints during human colonization. · 2020
  Not checked
• Cell biology of Candida albicans–host interactions · 2016
  No notice
• Metabolism impacts upon Candida immunogenicity and pathogenicity at multiple levels · 2014
  No notice
• Dietary carbohydrates modulate Candida albicans biofilm development on the denture surface. · 2013
  Not checked

Reads

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.