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Biofilm Development and Its Genetic Control

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  • Authors: Jigar V. Desai1, Aaron P. Mitchell2
  • Editors: Mahmoud Ghannoum3, Matthew Parsek4, Marvin Whiteley5, Pranab Mukherjee6
    Affiliations: 1: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213; 2: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213; 3: Case Western Reserve University, Cleveland, OH; 4: University of Washington, Seattle, WA; 5: University of Texas at Austin, Austin, TX; 6: Case Western Reserve University, Cleveland, OH
  • Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MB-0005-2014
  • Received 06 August 2014 Accepted 04 September 2014 Published 05 June 2015
  • Aaron Mitchell, [email protected]
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  • Abstract:

    The fungus is a major source of device-associated infection because of its capacity for biofilm formation. It is part of the natural mucosal flora and thus has access to available niches that can lead to infection. In this chapter we discuss the major properties of biofilms and the insight that has been gleaned from their genetic determinants. Our specific areas of focus include biofilm structure and development, cell morphology and biofilm formation, biofilm-associated gene expression, the cell surface and adherence, the extracellular matrix, biofilm metabolism, and biofilm drug resistance.

  • Citation: Desai J, Mitchell A. 2015. Biofilm Development and Its Genetic Control. Microbiol Spectrum 3(3):MB-0005-2014. doi:10.1128/microbiolspec.MB-0005-2014.


1. Finkel JS, Mitchell AP. 2011. Genetic control of Candida albicans biofilm development. Nat Rev Microbiol 9:109–118. [PubMed][CrossRef]
2. Kojic EM, Darouiche RO. 2004. Candida infections of medical devices. Clin Microbiol Rev 17:255–267. [CrossRef]
3. Marrie TJ, Costerton JW. 1984. Scanning and transmission electron microscopy of in situ bacterial colonization of intravenous and intraarterial catheters. J Clin Microbiol 19:687–693. [PubMed]
4. Hawser SP, Douglas LJ. 1994. Biofilm formation by Candida species on the surface of catheter materials in vitro. Infect Immun 62:915–921. [PubMed]
5. Berman J, Sudbery PE. 2002. Candida albicans: a molecular revolution built on lessons from budding yeast. Nat Rev Genet 3:918–930. [PubMed][CrossRef]
6. Daniels KJ, Park YN, Srikantha T, Pujol C, Soll DR. 2013. Impact of environmental conditions on the form and function of Candida albicans biofilms. Eukaryot Cell 12:1389–1402. [PubMed][CrossRef]
7. Chandra J, Kuhn DM, Mukherjee PK, Hoyer LL, McCormick T, Ghannoum MA. 2001. Biofilm formation by the fungal pathogen Candida albicans: development, architecture, and drug resistance. J Bacteriol 183:5385–5394. [PubMed][CrossRef]
8. Blankenship JR, Mitchell AP. 2006. How to build a biofilm: a fungal perspective. Curr Opin Microbiol 9:588–594. [PubMed][CrossRef]
9. Uppuluri P, Chaturvedi AK, Srinivasan A, Banerjee M, Ramasubramaniam AK, Kohler JR, Kadosh D, Lopez-Ribot JL. 2010. Dispersion as an important step in the Candida albicans biofilm developmental cycle. PLoS Pathog 6:e1000828. doi:10.1371/journal.ppat.1000828. [PubMed][CrossRef]
10. Tournu H, Van Dijck P. 2012. Candida biofilms and the host: models and new concepts for eradication. Int J Microbiol 2012:845352. [PubMed][CrossRef]
11. Chandra J, Long L, Ghannoum MA, Mukherjee PK. 2011. A rabbit model for evaluation of catheter-associated fungal biofilms. Virulence 2:466–474. [PubMed][CrossRef]
12. Andes D, Nett J, Oschel P, Albrecht R, Marchillo K, Pitula A. 2004. Development and characterization of an in vivo central venous catheter Candida albicans biofilm model. Infect Immun 72:6023–6031. [PubMed][CrossRef]
13. Wang X, Fries BC. 2011. A murine model for catheter-associated candiduria. J Med Microbiol 60:1523–1529. [PubMed][CrossRef]
14. Nett JE, Marchillo K, Spiegel CA, Andes DR. 2010. Development and validation of an in vivo Candida albicans biofilm denture model. Infect Immun 78:3650–3659. [PubMed][CrossRef]
15. Ganguly S, Mitchell AP. 2011. Mucosal biofilms of Candida albicans. Curr Opin Microbiol 14:380–385. [PubMed][CrossRef]
16. Baillie GS, Douglas LJ. 1999. Role of dimorphism in the development of Candida albicans biofilms. J Med Microbiol 48:671–679. [PubMed][CrossRef]
17. Richard ML, Nobile CJ, Bruno VM, Mitchell AP. 2005. Candida albicans biofilm-defective mutants. Eukaryot Cell 4:1493–1502. [PubMed][CrossRef]
18. Ramage G, VandeWalle K, Lopez-Ribot JL, Wickes BL. 2002. The filamentation pathway controlled by the Efg1 regulator protein is required for normal biofilm formation and development in Candida albicans. FEMS Microbiol Lett 214:95–100. [PubMed][CrossRef]
19. Nobile CJ, Mitchell AP. 2005. Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p. Curr Biol 15:1150–1155. [PubMed][CrossRef]
20. Nobile CJ, Andes DR, Nett JE, Smith FJ, Yue F, Phan QT, Edwards JE, Filler SG, Mitchell AP. 2006. Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation in vitro and in vivo. PLoS Pathog 2:e63. [PubMed][CrossRef]
21. Garcia-Sanchez S, Aubert S, Iraqui I, Janbon G, Ghigo JM, d'Enfert C. 2004. Candida albicans biofilms: a developmental state associated with specific and stable gene expression patterns. Eukaryot Cell 3:536–545. [PubMed][CrossRef]
22. Desai JV, Bruno VM, Ganguly S, Stamper RJ, Mitchell KF, Solis N, Hill EM, Xu W, Filler SG, Andes DR, Fanning S, Lanni F, Mitchell AP. 2013. Regulatory role of glycerol in Candida albicans biofilm formation. MBio 4:e00637-00612. doi:10.1128/mBio.00637-12. [PubMed][CrossRef]
23. Murillo LA, Newport G, Lan CY, Habelitz S, Dungan J, Agabian NM. 2005. Genome-wide transcription profiling of the early phase of biofilm formation by Candida albicans. Eukaryot Cell 4:1562–1573. [PubMed][CrossRef]
24. Yeater KM, Chandra J, Cheng G, Mukherjee PK, Zhao X, Rodriguez-Zas SL, Kwast KE, Ghannoum MA, Hoyer LL. 2007. Temporal analysis of Candida albicans gene expression during biofilm development. Microbiology 153:2373–2385. [PubMed][CrossRef]
25. Nett JE, Lepak AJ, Marchillo K, Andes DR. 2009. Time course global gene expression analysis of an in vivo Candida biofilm. J Infect Dis 200:307–313. [PubMed][CrossRef]
26. Bonhomme J, Chauvel M, Goyard S, Roux P, Rossignol T, d'Enfert C. 2011. Contribution of the glycolytic flux and hypoxia adaptation to efficient biofilm formation by Candida albicans. Mol Microbiol 80:995–1013. [PubMed][CrossRef]
27. Nobile CJ, Nett JE, Hernday AD, Homann OR, Deneault JS, Nantel A, Andes DR, Johnson AD, Mitchell AP. 2009. Biofilm matrix regulation by Candida albicans Zap1. PLoS Biol 7:e1000133. doi:10.1371/journal.pbio.1000133. [PubMed][CrossRef]
28. Taff HT, Nett JE, Zarnowski R, Ross KM, Sanchez H, Cain MT, Hamaker J, Mitchell AP, Andes DR. 2012. A Candida biofilm-induced pathway for matrix glucan delivery: implications for drug resistance. PLoS Pathog 8:e1002848. doi:10.1371/journal.ppat.1002848. [PubMed][CrossRef]
29. Nobile CJ, Fox EP, Nett JE, Sorrells TR, Mitrovich QM, Hernday AD, Tuch BB, Andes DR, Johnson AD. 2012. A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell 148:126–138. [PubMed][CrossRef]
30. Gow NA, Hube B. 2012. Importance of the Candida albicans cell wall during commensalism and infection. Curr Opin Microbiol 15:406–412. [PubMed][CrossRef]
31. Dranginis AM, Rauceo JM, Coronado JE, Lipke PN. 2007. A biochemical guide to yeast adhesins: glycoproteins for social and antisocial occasions. Microbiol Mol Biol Rev 71:282–294. [PubMed][CrossRef]
32. Chaffin WL. 2008. Candida albicans cell wall proteins. Microbiol Mol Biol Rev 72:495–544. [PubMed][CrossRef]
33. Hoyer LL, Green CB, Oh SH, Zhao X. 2008. Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family: a sticky pursuit. Med Mycol 46:1–15. [PubMed][CrossRef]
34. Li F, Palecek SP. 2003. EAP1, a Candida albicans gene involved in binding human epithelial cells. Eukaryot Cell 2:1266–1273. [PubMed][CrossRef]
35. Staab JF, Bradway SD, Fidel PL, Sundstrom P. 1999. Adhesive and mammalian transglutaminase substrate properties of Candida albicans Hwp1. Science 283:1535–1538. [PubMed][CrossRef]
36. Nobile CJ, Nett JE, Andes DR, Mitchell AP. 2006. Function of Candida albicans adhesin Hwp1 in biofilm formation. Eukaryot Cell 5:1604–1610. [PubMed][CrossRef]
37. Monniot C, Boisrame A, Da Costa G, Chauvel M, Sautour M, Bougnoux ME, Bellon-Fontaine MN, Dalle F, d'Enfert C, Richard ML. 2013. Rbt1 protein domains analysis in Candida albicans brings insights into hyphal surface modifications and Rbt1 potential role during adhesion and biofilm formation. PLoS One 8:e82395. doi:10.1371/journal.pone.0082395. [PubMed][CrossRef]
38. Granger BL, Flenniken ML, Davis DA, Mitchell AP, Cutler JE. 2005.Yeast wall protein 1 of Candida albicans. Microbiology 151:1631–1644. [PubMed][CrossRef]
39. Sandini S, Stringaro A, Arancia S, Colone M, Mondello F, Murtas S, Girolamo A, Mastrangelo N, De Bernardis F. 2011. The MP65 gene is required for cell wall integrity, adherence to epithelial cells and biofilm formation in Candida albicans. BMC Microbiol 11:106. [PubMed][CrossRef]
40. Singleton DR, Masuoka J, Hazen KC. 2001. Cloning and analysis of a Candida albicans gene that affects cell surface hydrophobicity. J Bacteriol 183:3582–3588. [PubMed][CrossRef]
41. Chaffin WL, Lopez-Ribot JL, Casanova M, Gozalbo D, Martinez JP. 1998. Cell wall and secreted proteins of Candida albicans: identification, function, and expression. Microbiol Mol Biol Rev 62:130–180. [PubMed]
42. Tronchin G, Bouchara JP, Robert R. 1989. Dynamic changes of the cell wall surface of Candida albicans associated with germination and adherence. Eur J Cell Biol 50:285–290. [PubMed]
43. Gaur NK, Klotz SA, Henderson RL. 1999. Overexpression of the Candida albicans ALA1 gene in Saccharomyces cerevisiae results in aggregation following attachment of yeast cells to extracellular matrix proteins, adherence properties similar to those of Candida albicans. Infect Immun 67:6040–6047. [PubMed]
44. Fu Y, Rieg G, Fonzi WA, Belanger PH, Edwards JE, Jr, Filler SG. 1998. Expression of the Candida albicans gene ALS1 in Saccharomyces cerevisiae induces adherence to endothelial and epithelial cells. Infect Immun 66:1783–1786. [PubMed]
45. Lipke PN, Garcia MC, Alsteens D, Ramsook CB, Klotz SA, Dufrene YF. 2012. Strengthening relationships: amyloids create adhesion nanodomains in yeasts. Trends Microbiol 20:59–65. [PubMed][CrossRef]
46. Hoyer LL, Hecht JE. 2001. The ALS5 gene of Candida albicans and analysis of the Als5p N-terminal domain. Yeast 18:49–60. [PubMed][CrossRef]
47. Salgado PS, Yan R, Taylor JD, Burchell L, Jones R, Hoyer LL, Matthews SJ, Simpson PJ, Cota E. 2011. Structural basis for the broad specificity to host-cell ligands by the pathogenic fungus Candida albicans. Proc Natl Acad Sci USA 108:15775–15779. [PubMed][CrossRef]
48. Klotz SA, Gaur NK, Lake DF, Chan V, Rauceo J, Lipke PN. 2004. Degenerate peptide recognition by Candida albicans adhesins Als5p and Als1p. Infect Immun 72:2029–2034. [PubMed][CrossRef]
49. Rauceo JM, De Armond R, Otoo H, Kahn PC, Klotz SA, Gaur NK, Lipke PN. 2006. Threonine-rich repeats increase fibronectin binding in the Candida albicans adhesin Als5p. Eukaryot Cell 5:1664–1673. [PubMed][CrossRef]
50. Nobile CJ, Schneider HA, Nett JE, Sheppard DC, Filler SG, Andes DR, Mitchell AP. 2008. Complementary adhesin function in C. albicans biofilm formation. Curr Biol 18:1017–1024. [PubMed][CrossRef]
51. Li F, Palecek SP. 2008. Distinct domains of the Candida albicans adhesin Eap1p mediate cell-cell and cell-substrate interactions. Microbiology 154:1193–1203. [PubMed][CrossRef]
52. Li F, Svarovsky MJ, Karlsson AJ, Wagner JP, Marchillo K, Oshel P, Andes D, Palecek SP. 2007. Eap1p, an adhesin that mediates Candida albicans biofilm formation in vitro and in vivo. Eukaryot Cell 6:931–939. [PubMed][CrossRef]
53. Ene IV, Bennett RJ. 2009. Hwp1 and related adhesins contribute to both mating and biofilm formation in Candida albicans. Eukaryot Cell 8:1909–1913. [PubMed][CrossRef]
54. Granger BL. 2012. Insight into the antiadhesive effect of yeast wall protein 1 of Candida albicans. Eukaryot Cell 11:795–805. [PubMed][CrossRef]
55. Biswas S, Van Dijck P, Datta A. 2007. Environmental sensing and signal transduction pathways regulating morphopathogenic determinants of Candida albicans. Microbiol Mol Biol Rev 71:348–376. [PubMed][CrossRef]
56. Finkel JS, Xu W, Huang D, Hill EM, Desai JV, Woolford CA, Nett JE, Taff H, Norice CT, Andes DR, Lanni F, Mitchell AP. 2012. Portrait of Candida albicans adherence regulators. PLoS Pathog 8:e1002525. doi:10.1371/journal.ppat.1002525. [PubMed][CrossRef]
57. Gutierrez-Escribano P, Zeidler U, Suarez MB, Bachellier-Bassi S, Clemente-Blanco A, Bonhomme J, Vazquez de Aldana CR, d'Enfert C, Correa-Bordes J. 2012. The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator Bcr1 during biofilm formation in Candida albicans. PLoS Pathog 8:e1002683. doi:10.1371/journal.ppat.1002683. [PubMed][CrossRef]
58. Bastidas RJ, Heitman J, Cardenas ME. 2009. The protein kinase Tor1 regulates adhesin gene expression in Candida albicans. PLoS Pathog 5:e1000294. doi:10.1371/journal.ppat.1000294. [PubMed][CrossRef]
59. Su C, Lu Y, Liu H. 2013. Reduced TOR signaling sustains hyphal development in Candida albicans by lowering Hog1 basal activity. Mol Biol Cell 24:385–397. [PubMed][CrossRef]
60. Shapiro RS, Robbins N, Cowen LE. 2011. Regulatory circuitry governing fungal development, drug resistance, and disease. Microbiol Mol Biol Rev 75:213–267. [PubMed][CrossRef]
61. Fanning S, Xu W, Beaurepaire C, Suhan JP, Nantel A, Mitchell AP. 2012. Functional control of the Candida albicans cell wall by catalytic protein kinase A subunit Tpk1. Mol Microbiol 86:284–302. [PubMed][CrossRef]
62. Sen M, Shah B, Rakshit S, Singh V, Padmanabhan B, Ponnusamy M, Pari K, Vishwakarma R, Nandi D, Sadhale PP. 2011. UDP-glucose 4, 6-dehydratase activity plays an important role in maintaining cell wall integrity and virulence of Candida albicans. PLoS Pathog 7:e1002384. doi:10.1371/journal.ppat.1002384. [PubMed][CrossRef]
63. Peltroche-Llacsahuanga H, Goyard S, d'Enfert C, Prill SK, Ernst JF. 2006. Protein O-mannosyltransferase isoforms regulate biofilm formation in Candida albicans. Antimicrob Agents Chemother 50:3488–3491. [PubMed][CrossRef]
64. Hiller E, Heine S, Brunner H, Rupp S. 2007. Candida albicans Sun41p, a putative glycosidase, is involved in morphogenesis, cell wall biogenesis, and biofilm formation. Eukaryot Cell 6:2056–2065. [PubMed][CrossRef]
65. Norice CT, Smith FJ, Jr, Solis N, Filler SG, Mitchell AP. 2007. Requirement for Candida albicans Sun41 in biofilm formation and virulence. Eukaryot Cell 6:2046–2055. [PubMed][CrossRef]
66. Hashash R, Younes S, Bahnan W, El Koussa J, Maalouf K, Dimassi HI, Khalaf RA. 2011. Characterisation of Pga1, a putative Candida albicans cell wall protein necessary for proper adhesion and biofilm formation. Mycoses 54:491–500. [PubMed][CrossRef]
67. Finkel JS, Yudanin N, Nett JE, Andes DR, Mitchell AP. 2011. Application of the systematic “DAmP” approach to create a partially defective C. albicans mutant. Fungal Genet Biol 48:1056–1061. [PubMed][CrossRef]
68. Liu Y, Filler SG. 2011. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell 10:168–173. [PubMed][CrossRef]
69. Zhao X, Oh SH, Yeater KM, Hoyer LL. 2005. Analysis of the Candida albicans Als2p and Als4p adhesins suggests the potential for compensatory function within the Als family. Microbiology 151:1619–1630. [PubMed][CrossRef]
70. Brand A, Lee K, Veses V, Gow NA. 2009. Calcium homeostasis is required for contact-dependent helical and sinusoidal tip growth in Candida albicans hyphae. Mol Microbiol 71:1155–1164. [PubMed][CrossRef]
71. Kumamoto CA. 2005. A contact-activated kinase signals Candida albicans invasive growth and biofilm development. Proc Natl Acad Sci USA 102:5576–5581. [PubMed][CrossRef]
72. Zucchi PC, Davis TR, Kumamoto CA. 2010. A Candida albicans cell wall-linked protein promotes invasive filamentation into semi-solid medium. Mol Microbiol 76:733–748. [PubMed][CrossRef]
73. Kumamoto CA. 2008. Molecular mechanisms of mechanosensing and their roles in fungal contact sensing. Nat Rev Microbiol 6:667–673. [PubMed][CrossRef]
74. Puri S, Kumar R, Chadha S, Tati S, Conti HR, Hube B, Cullen PJ, Edgerton M. 2012. Secreted aspartic protease cleavage of Candida albicans Msb2 activates Cek1 MAPK signaling affecting biofilm formation and oropharyngeal candidiasis. PLoS One 7:e46020. doi:10.1371/journal.pone.0046020. [PubMed][CrossRef]
75. Yi S, Sahni N, Daniels KJ, Pujol C, Srikantha T, Soll DR. 2008. The same receptor, G protein, and mitogen-activated protein kinase pathway activate different downstream regulators in the alternative white and opaque pheromone responses of Candida albicans. Mol Biol Cell 19:957–970. [PubMed][CrossRef]
76. Al-Fattani MA, Douglas LJ. 2006. Biofilm matrix of Candida albicans and Candida tropicalis: chemical composition and role in drug resistance. J Med Microbiol 55:999–1008. [PubMed][CrossRef]
77. Nett J, Lincoln L, Marchillo K, Massey R, Holoyda K, Hoff B, VanHandel M, Andes D. 2007. Putative role of beta-1,3 glucans in Candida albicans biofilm resistance. Antimicrob Agents Chemother 51:510–520. [PubMed][CrossRef]
78. Hawser SP, Baillie GS, Douglas LJ. 1998. Production of extracellular matrix by Candida albicans biofilms. J Med Microbiol 47:253–256. [PubMed][CrossRef]
79. Srikantha T, Daniels KJ, Pujol C, Kim E, Soll DR. 2013. Identification of genes upregulated by the transcription factor Bcr1 that are involved in impermeability, impenetrability, and drug resistance of Candida albicans a/alpha biofilms. Eukaryot Cell 12:875–888. [PubMed][CrossRef]
80. Nett JE, Sanchez H, Cain MT, Andes DR. 2010. Genetic basis of Candida biofilm resistance due to drug-sequestering matrix glucan. J Infect Dis 202:171–175. [PubMed][CrossRef]
81. Thomas DP, Bachmann SP, Lopez-Ribot JL. 2006. Proteomics for the analysis of the Candida albicans biofilm lifestyle. Proteomics 6:5795–5804. [PubMed][CrossRef]
82. Martins M, Uppuluri P, Thomas DP, Cleary IA, Henriques M, Lopez-Ribot JL, Oliveira R. 2010. Presence of extracellular DNA in the Candida albicans biofilm matrix and its contribution to biofilms. Mycopathologia 169:323–331. [PubMed][CrossRef]
83. Ganguly S, Bishop AC, Xu W, Ghosh S, Nickerson KW, Lanni F, Patton-Vogt J, Mitchell AP. 2011. Zap1 control of cell-cell signaling in Candida albicans biofilms. Eukaryot Cell 10:1448–1454. [PubMed][CrossRef]
84. Perez A, Pedros B, Murgui A, Casanova M, Lopez-Ribot JL, Martinez JP. 2006. Biofilm formation by Candida albicans mutants for genes coding fungal proteins exhibiting the eight-cysteine-containing CFEM domain. FEMS Yeast Res 6:1074–1084. [PubMed][CrossRef]
85. Weissman Z, Kornitzer D. 2004. A family of Candida cell surface haem-binding proteins involved in haemin and haemoglobin-iron utilization. Mol Microbiol 53:1209–1220. [PubMed][CrossRef]
86. Nett JE, Sanchez H, Cain MT, Ross KM, Andes DR. 2011. Interface of Candida albicans biofilm matrix-associated drug resistance and cell wall integrity regulation. Eukaryot Cell 10:1660–1669. [PubMed][CrossRef]
87. Robbins N, Uppuluri P, Nett J, Rajendran R, Ramage G, Lopez-Ribot JL, Andes D, Cowen LE. 2011. Hsp90 governs dispersion and drug resistance of fungal biofilms. PLoS Pathog 7:e1002257. doi:10.1371/journal.ppat.1002257. [PubMed][CrossRef]
88. Rossignol T, Ding C, Guida A, d'Enfert C, Higgins DG, Butler G. 2009. Correlation between biofilm formation and the hypoxic response in Candida parapsilosis. Eukaryot Cell 8:550–559. [PubMed][CrossRef]
89. Zhu Z, Wang H, Shang Q, Jiang Y, Cao Y, Chai Y. 2013. Time course analysis of Candida albicans metabolites during biofilm development. J Proteome Res 12:2375–2385. [PubMed][CrossRef]
90. Askew C, Sellam A, Epp E, Hogues H, Mullick A, Nantel A, Whiteway M. 2009. Transcriptional regulation of carbohydrate metabolism in the human pathogen Candida albicans. PLoS Pathog 5:e1000612. doi:10.1371/journal.ppat.1000612. [PubMed][CrossRef]
91. Stichternoth C, Ernst JF. 2009. Hypoxic adaptation by Efg1 regulates biofilm formation by Candida albicans. Appl Environ Microbiol 75:3663–3672. [PubMed][CrossRef]
92. Mukherjee PK, Mohamed S, Chandra J, Kuhn D, Liu S, Antar OS, Munyon R, Mitchell AP, Andes D, Chance MR, Rouabhia M, Ghannoum MA. 2006. Alcohol dehydrogenase restricts the ability of the pathogen Candida albicans to form a biofilm on catheter surfaces through an ethanol-based mechanism. Infect Immun 74:3804–3816. [PubMed][CrossRef]
93. Hornby JM, Jensen EC, Lisec AD, Tasto JJ, Jahnke B, Shoemaker R, Dussault P, Nickerson KW. 2001. Quorum sensing in the dimorphic fungus Candida albicans is mediated by farnesol. Appl Environ Microbiol 67:2982–2992. [PubMed][CrossRef]
94. Ramage G, Saville SP, Wickes BL, Lopez-Ribot JL. 2002. Inhibition of Candida albicans biofilm formation by farnesol, a quorum-sensing molecule. Appl Environ Microbiol 68:5459–5463. [PubMed][CrossRef]
95. Lindsay AK, Deveau A, Piispanen AE, Hogan DA. 2012. Farnesol and cyclic AMP signaling effects on the hypha-to-yeast transition in Candida albicans. Eukaryot Cell 11:1219–1225. [PubMed][CrossRef]
96. Lu Y, Su C, Unoje O, Liu H. 2014. Quorum sensing controls hyphal initiation in Candida albicans through Ubr1-mediated protein degradation. Proc Natl Acad Sci USA 111:1975–1980. [PubMed][CrossRef]
97. Hohmann S. 2002. Osmotic stress signaling and osmo adaptation in yeasts. Microbiol Mol Biol Rev 66:300–372. [PubMed][CrossRef]
98. Nett JE, Crawford K, Marchillo K, Andes DR. 2010. Role of Fks1p and matrix glucan in Candida albicans biofilm resistance to an echinocandin, pyrimidine, and polyene. Antimicrob Agents Chemother 54:3505–3508. [PubMed][CrossRef]
99. Martins M, Henriques M, Lopez-Ribot JL, Oliveira R. 2012. Addition of DNase improves the in vitro activity of antifungal drugs against Candida albicans biofilms. Mycoses 55:80–85. [PubMed][CrossRef]
100. Mukherjee PK, Chandra J, Kuhn DM, Ghannoum MA. 2003. Mechanism of fluconazole resistance in Candida albicans biofilms: phase-specific role of efflux pumps and membrane sterols. Infect Immun 71:4333–4340. [PubMed][CrossRef]
101. Ramage G, Bachmann S, Patterson TF, Wickes BL, Lopez-Ribot JL. 2002. Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms. J Antimicrob Chemother 49:973–980. [PubMed][CrossRef]
102. LaFleur MD, Kumamoto CA, Lewis K. 2006. Candida albicans biofilms produce antifungal-tolerant persister cells. Antimicrob Agents Chemother 50:3839–3846. [PubMed][CrossRef]
103. Bink A, Vandenbosch D, Coenye T, Nelis H, Cammue BP, Thevissen K. 2011. Superoxide dismutases are involved in Candida albicans biofilm persistence against miconazole. Antimicrob Agents Chemother 55:4033–4037. [PubMed][CrossRef]
104. Stewart PS, Franklin MJ. 2008. Physiological heterogeneity in biofilms. Nat Rev Microbiol 6:199–210. [PubMed][CrossRef]
105. Nett JE, Andes DR. 2015. Fungal Biofilms: In Vivo Models for Discovery of Anti-Biofilm Drugs. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, 2nd ed. ASM Press, Washington, DC, in press.

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The fungus is a major source of device-associated infection because of its capacity for biofilm formation. It is part of the natural mucosal flora and thus has access to available niches that can lead to infection. In this chapter we discuss the major properties of biofilms and the insight that has been gleaned from their genetic determinants. Our specific areas of focus include biofilm structure and development, cell morphology and biofilm formation, biofilm-associated gene expression, the cell surface and adherence, the extracellular matrix, biofilm metabolism, and biofilm drug resistance.

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Confocal micrographic images of a biofilm. These images present a biofilm grown in yeast extract-peptone-dextrose medium at 37°C. The sample was prepared by embedding and staining with Alexafluor 594-conjugated Concanavalin A, using a procedure modified from reference 83 . (A) Side projection view. Hyphae are clearly visible in the upper portion of the biofilm, as are aggregates of brightly stained extracellular material. A color scale bar represents the 270-micron depth and indicates the pseudocolor scale used for apical projections. (B) Apical projection of basal (substrate-proximal) 50-micron region. A yeast cell layer is evident from the substrate level (red) to 50 microns above the substrate (blue). A few hyphae or pseudohyphae are visible as well. Some amorphous extracellular material is apparent. (C) Apical projection of the entire biofilm. Hyphae are visible above the basal layer, extending from ∼150 microns (green) to 270 microns (red) above the substrate. Yeast cells are seen in clusters at the ends of hyphae. (D) Three-dimensional reconstruction of the biofilm sample. Hyphae at the top of the biofilm are readily visible above the dense basal region.

Source: microbiolspec June 2015 vol. 3 no. 3 doi:10.1128/microbiolspec.MB-0005-2014
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