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The role of iron in Mycobacterium smegmatis biofilm formation: the exochelin siderophore is essential in limiting iron conditions for biofilm formation but not for planktonic growth

Anil Ojha, Graham F. Hatfull

Molecular Microbiology · 2007

doi:10.1111/j.1365-2958.2007.05935.x

Abstract

Summary Many species of mycobacteria form structured biofilm communities at liquid–air interfaces and on solid surfaces. Full development of Mycobacterium smegmatis biofilms requires addition of supplemental iron above 1 μM ferrous sulphate, although addition of iron is not needed for planktonic growth. Microarray analysis of the M. smegmatis transcriptome shows that iron‐responsive genes – especially those involved in siderophore synthesis and iron uptake – are strongly induced during biofilm formation reflecting a response to iron deprivation, even when 2 μM iron is present. The acquisition of iron under these conditions is specifically dependent on the exochelin synthesis and uptake pathways, and the strong defect of an iron–exochelin uptake mutant suggests a regulatory role of iron in the transition to biofilm growth. In contrast, although the expression of mycobactin and iron ABC transport operons is highly upregulated during biofilm formation, mutants in these systems form normal biofilms in low‐iron (2 μM) conditions. A close correlation between iron availability and matrix‐associated fatty acids implies a possible metabolic role in the late stages of biofilm maturation, in addition to the early regulatory role. M. smegmatis surface motility is similarly dependent on iron availability, requiring both supplemental iron and the exochelin pathway to acquire it.

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References 65

  1. 1.

    Andrews SC, Robinson AK, Rodriguez-Quinones F. Bacterial iron homeostasis. FEMS Microbiol Rev. 2003;27:215-237.

    Not in our library10.1016/s0168-6445(03)00055-x

  2. 2.

    Banin E, Vasil ML, Greenberg EP. Iron and Pseudomonas aeruginosa biofilm formation. Proc Natl Acad Sci USA. 2005;102:11076-11081.

    Not in our library10.1073/pnas.0504266102

  3. 3.

    Bardarov S, Bardarov S, Pavelka MS, Sambandamurthy V, Larsen M, Tufariello J, et al. Specialized transduction: an efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis, M. bovis BCG and M. smegmatis. Microbiology. 2002;148:3007-3017.

    Not in our library10.1099/00221287-148-10-3007

  4. 4.

    Beenken KE, Dunman PM, McAleese F, Macapagal D, Murphy E, Projan SJ, et al. Global gene expression in Staphylococcus aureus biofilms. J Bacteriol. 2004;186:4665-4684.

    Not in our library10.1128/jb.186.14.4665-4684.2004

  5. 5.

    Beloin C, Ghigo JM. Finding gene-expression patterns in bacterial biofilms. Trends Microbiol. 2005;13:16-19.

    Not in our library10.1016/j.tim.2004.11.008

  6. 6.

    Beloin C, Valle J, Latour-Lambert P, Faure P, Kzreminski M, Balestrino D, et al. Global impact of mature biofilm lifestyle on Escherichia coli K-12 gene expression. Mol Microbiol. 2004;51:659-674.

    Not in our library10.1046/j.1365-2958.2003.03865.x

  7. 7.

    Berlutti F, Morea C, Battistoni A, Sarli S, Cipriani P, Superti F, et al. Iron availability influences aggregation, biofilm, adhesion and invasion of Pseudomonas aeruginosa and Burkholderia cenocepacia. Int J Immunopathol Pharmacol. 2005;18:661-670.

    Not in our library10.1177/039463200501800407

  8. 8.

    Billman-Jacobe H, McConville MJ, Haites RE, Kovacevic S, Coppel RL. Identification of a peptide synthetase involved in the biosynthesis of glycopeptidolipids of Mycobacterium smegmatis. Mol Microbiol. 1999;33:1244-1253.

    Not in our library10.1046/j.1365-2958.1999.01572.x

  9. 9.

    Carter G, Wu M, Drummond DC, Bermudez LE. Characterization of biofilm formation by clinical isolates of Mycobacterium avium. J Med Microbiol. 2003;52:747-752.

    Not in our library10.1099/jmm.0.05224-0

  10. 10.

    Cho KH, Caparon MG. Patterns of virulence gene expression differ between biofilm and tissue communities of Streptococcus pyogenes. Mol Microbiol. 2005;57:1545-1556.

    Not in our library10.1111/j.1365-2958.2005.04786.x

  11. 11.

    Costerton JW, Stewart PS, Greenberg EP. Bacterial biofilms: a common cause of persistent infections. Science. 1999;284:1318-1322.

    Not in our library10.1126/science.284.5418.1318

  12. 12.

    Davey ME, O'Toole GA. Microbial biofilms: from ecology to molecular genetics. Microbiol Mol Biol Rev. 2000;64:847-867.

    Not in our library10.1128/mmbr.64.4.847-867.2000

  13. 13.

    De Voss JJ, Rutter K, Schroeder BG, Barry CE. Iron acquisition and metabolism by mycobacteria. J Bacteriol. 1999;181:4443-4451.

    Not in our library10.1128/jb.181.15.4443-4451.1999

  14. 14.
  15. 15.

    Domka J, Lee J, Bansal T, Wood TK. Temporal gene-expression in Escherichia coli K-12 biofilms. Environ Microbiol. 2007;9:332-346.

    Not in our library10.1111/j.1462-2920.2006.01143.x

  16. 16.

    Dussurget O, Rodriguez M, Smith I. An ideR mutant of Mycobacterium smegmatis has derepressed siderophore production and an altered oxidative-stress response. Mol Microbiol. 1996;22:535-544.

    Not in our library10.1046/j.1365-2958.1996.1461511.x

  17. 17.

    Fiss EH, Yu S, Jacobs WR. Identification of genes involved in the sequestration of iron in mycobacteria: the ferric exochelin biosynthetic and uptake pathways. Mol Microbiol. 1994;14:557-569.

    Not in our library10.1111/j.1365-2958.1994.tb02189.x

  18. 18.

    Frieden TR, Driver CR. Tuberculosis control: past 10 years and future progress. Tuberculosis (Edinb). 2003;83:82-85.

    Not in our library10.1016/s1472-9792(02)00060-4

  19. 19.

    Gomez JE, McKinney JD. M. tuberculosis persistence, latency, and drug tolerance. Tuberculosis (Edinb). 2004;84:29-44.

    Not in our library10.1016/j.tube.2003.08.003

  20. 20.

    Hall-Stoodley L, Lappin-Scott H. Biofilm formation by the rapidly growing mycobacterial species Mycobacterium fortuitum. FEMS Microbiol Lett. 1998;168:77-84.

    Not in our library10.1111/j.1574-6968.1998.tb13258.x

  21. 21.

    Hall-Stoodley L, Costerton JW, Stoodley P. Bacterial biofilms: from the natural environment to infectious diseases. Nat Rev Microbiol. 2004;2:95-108.

    Not in our library10.1038/nrmicro821

  22. 22.

    Hall-Stoodley L, Brun OS, Polshyna G, Barker LP. Mycobacterium marinum biofilm formation reveals cording morphology. FEMS Microbiol Lett. 2006;257:43-49.

    Not in our library10.1111/j.1574-6968.2006.00143.x

  23. 23.

    Honer Zu Bentrup K, Miczak A, Swenson DL, Russell DG. Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J Bacteriol. 1999;181:7161-7167.

    Not in our library10.1128/jb.181.23.7161-7167.1999

  24. 24.

    Jeevarajah D, Patterson JH, McConville MJ, Billman-Jacobe H. Modification of glycopeptidolipids by an O-methyltransferase of Mycobacterium smegmatis. Microbiology. 2002;148:3079-3087.

    Not in our library10.1099/00221287-148-10-3079

  25. 25.

    van Kessel JC, Hatfull GF. Recombineering in Mycobacterium tuberculosis. Nat Methods. 2007;4:147-152.

    Not in our library10.1038/nmeth996

  26. 26.

    Krithika R, Marathe U, Saxena P, Ansari MZ, Mohanty D, Gokhale RS. A genetic locus required for iron acquisition in Mycobacterium tuberculosis. Proc Natl Acad Sci USA. 2006;103:2069-2074.

    Not in our library10.1073/pnas.0507924103

  27. 27.

    LaMarca BB, Zhu W, Arceneaux JE, Byers BR, Lundrigan MD. Participation of fad and mbt genes in synthesis of mycobactin in Mycobacterium smegmatis. J Bacteriol. 2004;186:374-382.

    Not in our library10.1128/jb.186.2.374-382.2004

  28. 28.

    Lazazzera BA. Lessons from DNA microarray analysis: the gene expression profile of biofilms. Curr Opin Microbiol. 2005;8:222-227.

    Not in our library10.1016/j.mib.2005.02.015

  29. 29.

    McCune RM, Feldmann FM, Lambert HP, McDermott W. Microbial persistence. I. The capacity of tubercle bacilli to survive sterilization in mouse tissues. J Exp Med. 1966;123:445-468.

    Not in our library10.1084/jem.123.3.445

  30. 30.

    Marsollier L, Aubry J, Coutanceau E, Andre JP, Small PL, Milon G, et al. Colonization of the salivary glands of Naucoris cimicoides by Mycobacterium ulcerans requires host plasmatocytes and a macrolide toxin, mycolactone. Cell Microbiol. 2005;7:935-943.

    Not in our library10.1111/j.1462-5822.2005.00521.x

  31. 31.

    Martinez A, Torello S, Kolter R. Sliding motility in mycobacteria. J Bacteriol. 1999;181:7331-7338.

    Not in our library10.1128/jb.181.23.7331-7338.1999

  32. 32.

    Milano A, Forti F, Sala C, Riccardi G, Ghisotti D. Transcriptional regulation of furA and katG upon oxidative stress in Mycobacterium smegmatis. J Bacteriol. 2001;183:6801-6806.

    Not in our library10.1128/jb.183.23.6801-6806.2001

  33. 33.

    Moorthy S, Watnick PI. Identification of novel stage-specific genetic requirements through whole genome transcription profiling of Vibrio cholerae biofilm development. Mol Microbiol. 2005;57:1623-1635.

    Not in our library10.1111/j.1365-2958.2005.04797.x

  34. 34.

    O'Toole G, Kaplan HB, Kolter R. Biofilm formation as microbial development. Annu Rev Microbiol. 2000;54:49-79.

    Not in our library10.1146/annurev.micro.54.1.49

  35. 35.

    Ojha A, Anand M, Bhatt A, Kremer L, Jacobs WR, Hatfull GF. GroEL1: a dedicated chaperone involved in mycolic acid biosynthesis during biofilm formation in mycobacteria. Cell. 2005;123:861-873.

    Not in our library10.1016/j.cell.2005.09.012

  36. 36.

    Ojha AK, Varma S, Chatterji D. Synthesis of an unusual polar glycopeptidolipid in glucose-limited culture of Mycobacterium smegmatis. Microbiology. 2002;148:3039-3048.

    Not in our library10.1099/00221287-148-10-3039

  37. 37.

    Panina EM, Mironov AA, Gelfand MS. Comparative genomics of bacterial zinc regulons: enhanced ion transport, pathogenesis, and rearrangement of ribosomal proteins. Proc Natl Acad Sci USA. 2003;100:9912-9917.

    Not in our library10.1073/pnas.1733691100

  38. 38.

    Patterson JH, McConville MJ, Haites RE, Coppel RL, Billman-Jacobe H. Identification of a methyltransferase from Mycobacterium smegmatis involved in glycopeptidolipid synthesis. J Biol Chem. 2000;275:24900-24906.

    Not in our library10.1074/jbc.m000147200

  39. 39.

    Pruss BM, Besemann C, Denton A, Wolfe AJ. A complex transcription network controls the early stages of biofilm development by Escherichia coli. J Bacteriol. 2006;188:3731-3739.

    Not in our library10.1128/jb.01780-05

  40. 40.

    Pysz MA, Conners SB, Montero CI, Shockley KR, Johnson MR, Ward DE, Kelly RM. Transcriptional analysis of biofilm formation processes in the anaerobic, hyperthermophilic bacterium Thermotoga maritima. Appl Environ Microbiol. 2004;70:6098-6112.

    Not in our library10.1128/aem.70.10.6098-6112.2004

  41. 41.

    Recht J, Kolter R. Glycopeptidolipid acetylation affects sliding motility and biofilm formation in Mycobacterium smegmatis. J Bacteriol. 2001;183:5718-5724.

    Not in our library10.1128/jb.183.19.5718-5724.2001

  42. 42.

    Recht J, Martinez A, Torello S, Kolter R. Genetic analysis of sliding motility in Mycobacterium smegmatis. J Bacteriol. 2000;182:4348-4351.

    Not in our library10.1128/jb.182.15.4348-4351.2000

  43. 43.

    Ren D, Bedzyk LA, Thomas SM, Ye RW, Wood TK. Gene expression in Escherichia coli biofilms. Appl Microbiol Biotechnol. 2004a;64:515-524.

    Not in our library10.1007/s00253-003-1517-y

  44. 44.

    Ren D, Bedzyk LA, Setlow P, Thomas SM, Ye RW, Wood TK. Gene expression in Bacillus subtilis surface biofilms with and without sporulation and the importance of yveR for biofilm maintenance. Biotechnol Bioeng. 2004b;86:344-364.

    Not in our library10.1002/bit.20053

  45. 45.

    Rodriguez GM, Smith I. Mechanisms of iron regulation in mycobacteria: role in physiology and virulence. Mol Microbiol. 2003;47:1485-1494.

    Not in our library10.1046/j.1365-2958.2003.03384.x

  46. 46.

    Rodriguez GM, Voskuil MI, Gold B, Schoolnik GK, Smith I. ideR, an essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect Immun. 2002;70:3371-3381.

    Not in our library10.1128/iai.70.7.3371-3381.2002

  47. 47.

    Rose L, Kaufmann SH, Daugelat S. Involvement of Mycobacterium smegmatis undecaprenyl phosphokinase in biofilm and smegma formation. Microbes Infect. 2004;6:965-971.

    Not in our library10.1016/j.micinf.2004.05.011

  48. 48.

    Sala C, Forti F, Di Florio E, Canneva F, Milano A, Riccardi G, Ghisotti D. Mycobacterium tuberculosis FurA autoregulates its own expression. J Bacteriol. 2003;185:5357-5362.

    Not in our library10.1128/jb.185.18.5357-5362.2003

  49. 49.

    Sampathkumar B, Napper S, Carrillo CD, Willson P, Taboada E, Nash JH, et al. Transcriptional and translational expression patterns associated with immobilized growth of Campylobacter jejuni. Microbiology. 2006;152:567-577.

    Not in our library10.1099/mic.0.28405-0

  50. 50.

    Schembri MA, Kjaergaard K, Klemm P. Global gene expression in Escherichia coli biofilms. Mol Microbiol. 2003;48:253-267.

    Not in our library10.1046/j.1365-2958.2003.03432.x

  51. 51.

    Singh PK, Parsek MR, Greenberg EP, Welsh MJ. A component of innate immunity prevents bacterial biofilm development. Nature. 2002;417:552-555.

    Not in our library10.1038/417552a

  52. 52.

    de Souza AA, Takita MA, Coletta-Filho HD, Caldana C, Yanai GM, Muto NH, et al. Gene expression profile of the plant pathogen Xylella fastidiosa during biofilm formation in vitro. FEMS Microbiol Lett. 2004;237:341-353.

    Not in our library10.1016/j.femsle.2004.06.055

  53. 53.

    de Souza AA, Takita MA, Pereira EO, Coletta-Filho HD, Machado MA. Expression of pathogenicity-related genes of Xylella fastidiosa in vitro and in planta. Curr Microbiol. 2005;50:223-228.

    Not in our library10.1007/s00284-004-4447-8

  54. 54.

    Stanley NR, Britton RA, Grossman AD, Lazazzera BA. Identification of catabolite repression as a physiological regulator of biofilm formation by Bacillus subtilis by use of DNA microarrays. J Bacteriol. 2003;185:1951-1957.

    Not in our library10.1128/jb.185.6.1951-1957.2003

  55. 55.

    Stewart GR, Robertson BD, Young DB. Tuberculosis: a problem with persistence. Nat Rev Microbiol. 2003;1:97-105.

    Not in our library10.1038/nrmicro749

  56. 56.

    Teng R, Dick T. Isoniazid resistance of exponentially growing Mycobacterium smegmatis biofilm culture. FEMS Microbiol Lett. 2003;227:171-174.

    Not in our library10.1016/s0378-1097(03)00584-6

  57. 57.

    Timm J, Post FA, Bekker LG, Walther GB, Wainwright HC, Manganelli R, et al. Differential expression of iron-, carbon-, and oxygen-responsive mycobacterial genes in the lungs of chronically infected mice and tuberculosis patients. Proc Natl Acad Sci USA. 2003;100:14321-14326.

    Not in our library10.1073/pnas.2436197100

  58. 58.

    Waite RD, Papakonstantinopoulou A, Littler E, Curtis MA. Transcriptome analysis of Pseudomonas aeruginosa growth: comparison of gene expression in planktonic cultures and developing and mature biofilms. J Bacteriol. 2005;187:6571-6576.

    Not in our library10.1128/jb.187.18.6571-6576.2005

  59. 59.

    Waite RD, Paccanaro A, Papakonstantinopoulou A, Hurst JM, Saqi M, Littler E, Curtis MA. Clustering of Pseudomonas aeruginosa transcriptomes from planktonic cultures, developing and mature biofilms reveals distinct expression profiles. BMC Genomics. 2006;7:162.

    Not in our library10.1186/1471-2164-7-162

  60. 60.

    Whiteley M, Bangera MG, Bumgarner RE, Parsek MR, Teitzel GM, Lory S, Greenberg EP. Gene expression in Pseudomonas aeruginosa biofilms. Nature. 2001;413:860-864.

    Not in our library10.1038/35101627

  61. 61.

    Wisedchaisri G, Chou CJ, Wu M, Roach C, Rice AE, Holmes RK, et al. Crystal structures, metal activation, and DNA-binding properties of two-domain IdeR from Mycobacterium tuberculosis. Biochemistry. 2007;46:436-447.

    Not in our library10.1021/bi0609826

  62. 62.

    Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J, Speed TP. Normalization for cDNA microarray data: a robust composite method addressing single and multiple slide systematic variation. Nucleic Acids Res. 2002;30:e15.

    Not in our library10.1093/nar/30.4.e15

  63. 63.

    Yu S, Fiss E, Jacobs WR. Analysis of the exochelin locus in Mycobacterium smegmatis: biosynthesis genes have homology with genes of the peptide synthetase family. J Bacteriol. 1998;180:4676-4685.

    Not in our library10.1128/jb.180.17.4676-4685.1998

  64. 64.

    Zahrt TC, Song J, Siple J, Deretic V. Mycobacterial FurA is a negative regulator of catalase-peroxidase gene katG. Mol Microbiol. 2001;39:1174-1185.

    Not in our library10.1111/j.1365-2958.2001.02321.x

  65. 65.

    Zambrano MM, Kolter R. Mycobacterial biofilms: a greasy way to hold it together. Cell. 2005;123:762-764.

    Not in our library10.1016/j.cell.2005.11.011

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