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The filamentation pathway controlled by the Efg1 regulator protein is required for normal biofilm formation and development in Candida albicans
Abstract
Candida albicans biofilms are structured microbial communities composed of a mixture of yeast cells and hyphal elements, suggesting a pivotal role for the dimorphic switch in the development of biofilms. We have used C. albicans mutants defective in genes involved in filamentation (Δcph1, Δefg1, Δhst7, and Δcst20) and compared these mutants to wild-type strains to determine whether filamentation is an integral factor for biofilm formation. Scanning electron microscopy revealed that Δcph1, Δhst7 and Δcst20 mutants were able to filament and form structured biofilms displaying three-dimensional architecture similar to those formed by wild-type strains. However, Δefg1 and Δcph1/Δefg1 mutants were unable to filament and did not form biofilms, but rather sparse monolayers of loosely attached elongated, rod-like, cells. Antimicrobial susceptibility testing showed intrinsic resistance of all mutant strains to fluconazole and amphotericin B when attached to the surface of biomaterials. These results suggest that hyphal formation is pivotal for biofilm development in C. albicans. However, the sessile lifestyle associated with adherent cells confers antifungal resistance, regardless of coherent biofilm formation.
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“Although they readily form in planktonic cultures, hyphae are an important structural component of C. albicans biofilms; thus, it is not surprising that genes required for hyphal growth in suspension cultures are also necessary for proper biofilm formation.”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [163]
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Cites
Nonfilamentous C. albicans Mutants Are Avirulent
Lo, H.-J., Köhler, J. R., DiDomenico, B., Loebenberg, D., Cacciapuoti, A., & Fink, G. R. (1997) · Cell · doi:10.1016/s0092-8674(00)80358-x · Cited by 1,809
Isogenic strain construction and gene mapping in Candida albicans.
Fonzi, W. A., & Irwin, M. Y. (1993) · Genetics · doi:10.1093/genetics/134.3.717 · Cited by 1,695
Gimeno, C. J., Ljungdahl, P. O., Styles, C. A., & Fink, G. R. (1992) · Cell · doi:10.1016/0092-8674(92)90079-r · Cited by 1,180
Suppression of Hyphal Formation in Candida albicans by Mutation of a STE12 Homolog
Liu, H., Köhler, J. R., & Fink, G. R. (1994) · Science · doi:10.1126/science.7992058 · Cited by 788
Standardized Method for In Vitro Antifungal Susceptibility Testing of Candida albicans Biofilms
Ramage, G., Vande Walle, K., Wickes, B. L., & López-Ribot, J. L. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.9.2475-2479.2001 · Cited by 753
Self-citationRoberts, R. L., & Fink, G. R. (1994) · Genes & Development · doi:10.1101/gad.8.24.2974 · Cited by 616
Stoldt, V. R., Sonneborn, A., Leuker, C. E., & Ernst, J. F. (1997) · The EMBO Journal · doi:10.1093/emboj/16.8.1982 · Cited by 595
Elements of the Yeast Pheromone Response Pathway Required for Filamentous Growth of Diploids
Liu, H., Styles, C. A., & Fink, G. R. (1993) · Science · doi:10.1126/science.8259520 · Cited by 500
Ramage, G. (2002) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkf049 · Cited by 468
Self-citationRas Signaling Is Required for Serum-Induced Hyphal Differentiation in Candida albicans
Feng, Q., Summers, E., Guo, B., & Fink, G. R. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.20.6339-6346.1999 · Cited by 347
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Candida biofilms and their role in infection
Douglas, L. J. (2003) · Trends in Microbiology · doi:10.1016/s0966-842x(02)00002-1 · Cited by 1,150
Candida albicans Biofilms and Human Disease
Nobile, C. J., & Johnson, A. D. (2015) · Annual Review of Microbiology · doi:10.1146/annurev-micro-091014-104330 · Cited by 1,057
Candida albicans biofilms: development, regulation, and molecular mechanisms
Gulati, M., & Nobile, C. J. (2016) · Microbes and Infection · doi:10.1016/j.micinf.2016.01.002 · Cited by 738
A Recently Evolved Transcriptional Network Controls Biofilm Development in Candida albicans
Nobile, C. J., Fox, E. P., Nett, J. E., Sorrells, T. R., Mitrovich, Q. M., Hernday, A. D., Tuch, B. B., Andes, D. R., & Johnson, A. D. (2012) · Cell · doi:10.1016/j.cell.2011.10.048 · Cited by 711
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Cavalheiro, M., & Teixeira, M. C. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00028 · Cited by 690
Ramage, G., Saville, S. P., Thomas, D. P., & López-Ribot, J. L. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.4.633-638.2005 · Cited by 678
Self-citationRamage, G., Rajendran, R., Sherry, L., & Williams, C. (2012) · International Journal of Microbiology · doi:10.1155/2012/528521 · Cited by 583
Self-citationCandida biofilms on implanted biomaterials: a clinically significant problem
Ramage, G., MartÃnez, J. P., & López-Ribot, J. L. (2006) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2006.00117.x · Cited by 575
Self-citationHow to build a biofilm: a fungal perspective
Blankenship, J. R., & Mitchell, A. P. (2006) · Current Opinion in Microbiology · doi:10.1016/j.mib.2006.10.003 · Cited by 530
Candida albicans Biofilms Produce Antifungal-Tolerant Persister Cells
LaFleur, M. D., Kumamoto, C. A., & Lewis, K. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00684-06 · Cited by 521
Our Current Understanding of Fungal Biofilms
Ramage, G., Mowat, E., Jones, B., Williams, C., & Lopez-Ribot, J. (2009) · Critical Reviews in Microbiology · doi:10.3109/10408410903241436 · Cited by 483
Self-citationDenture stomatitis: a role for Candida biofilms
Ramage, G., Tomsett, K., Wickes, B. L., López-Ribot, J. L., & Redding, S. W. (2004) · Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology · doi:10.1016/j.tripleo.2003.04.002 · Cited by 489
Self-citationRegulation of Cell-Surface Genes and Biofilm Formation by the C. albicans Transcription Factor Bcr1p
Nobile, C. J., & Mitchell, A. P. (2005) · Current Biology · doi:10.1016/j.cub.2005.05.047 · Cited by 464
Dispersion as an Important Step in the Candida albicans Biofilm Developmental Cycle
Uppuluri, P., Chaturvedi, A. K., Srinivasan, A., Banerjee, M., Ramasubramaniam, A. K., Köhler, J. R., Kadosh, D., & Lopez-Ribot, J. L. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000828 · Cited by 432
Andes, D., Nett, J., Oschel, P., Albrecht, R., Marchillo, K., & Pitula, A. (2004) · Infection and Immunity · doi:10.1128/iai.72.10.6023-6031.2004 · Cited by 389
García-Sánchez, S., Aubert, S., Iraqui, I., Janbon, G., Ghigo, J.-M., & d'Enfert, C. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.2.536-545.2004 · Cited by 353
Biofilm lifestyle of Candida: a mini review
Seneviratne, C., Jin, L., & Samaranayake, L. (2008) · Oral Diseases · doi:10.1111/j.1601-0825.2007.01424.x · Cited by 317
Candida albicans forms biofilms on the vaginal mucosa
Harriott, M. M., Lilly, E. A., Rodriguez, T. E., Fidel, P. L., & Noverr, M. C. (2010) · Microbiology · doi:10.1099/mic.0.039354-0 · Cited by 301
“These mutants have previously been shown to form poor or no biofilms on abiotic surfaces (Nobile et al., 2006a, b; Nobile & Mitchell, 2005; Ramage et al., 2002).”
InfluentialHsp90 Governs Dispersion and Drug Resistance of Fungal Biofilms
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Self-citationCandida albicans biofilm growth and dispersal: contributions to pathogenesis
Wall, G., Montelongo-Jauregui, D., Vidal Bonifacio, B., Lopez-Ribot, J. L., & Uppuluri, P. (2019) · Current Opinion in Microbiology · doi:10.1016/j.mib.2019.04.001 · Cited by 263
Fungal Biofilms, Drug Resistance, and Recurrent Infection
Desai, J. V., Mitchell, A. P., & Andes, D. R. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019729 · Cited by 252
Graham, C. E., Cruz, M. R., Garsin, D. A., & Lorenz, M. C. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620432114 · Cited by 239
ALTERNATIVECANDIDA ALBICANSLIFESTYLES: Growth on Surfaces
Kumamoto, C. A., & Vinces, M. D. (2005) · Annual Review of Microbiology · doi:10.1146/annurev.micro.59.030804.121034 · Cited by 247
Hwang, G., Liu, Y., Kim, D., Li, Y., Krysan, D. J., & Koo, H. (2017) · PLOS Pathogens · doi:10.1371/journal.ppat.1006407 · Cited by 214
Candida albicans biofilm development, modeling a host–pathogen interaction
Nett, J., & Andes, D. (2006) · Current Opinion in Microbiology · doi:10.1016/j.mib.2006.06.007 · Cited by 210
Mucosal biofilms of Candida albicans
Ganguly, S., & Mitchell, A. P. (2011) · Current Opinion in Microbiology · doi:10.1016/j.mib.2011.06.001 · Cited by 200
Radhakrishnan, V. S., Mudiam, M. K. R., Kumar, M., Dwivedi, S. P., Singh, S. P., & Prasad, T. (2018) · International Journal of Nanomedicine · doi:10.2147/ijn.s150648 · Cited by 184
Antifungal therapy with an emphasis on biofilms
Pierce, C. G., Srinivasan, A., Uppuluri, P., Ramasubramanian, A. K., & López-Ribot, J. L. (2013) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2013.08.008 · Cited by 173
The Candida albicans CaACE2 gene affects morphogenesis, adherence and virulence
Kelly, M. T., MacCallum, D. M., Clancy, S. D., Odds, F. C., Brown, A. J. P., & Butler, G. (2004) · Molecular Microbiology · doi:10.1111/j.1365-2958.2004.04185.x · Cited by 175
An expanded regulatory network temporally controls C andida albicans biofilm formation
Fox, E. P., Bui, C. K., Nett, J. E., Hartooni, N., Mui, M. C., Andes, D. R., Nobile, C. J., & Johnson, A. D. (2015) · Molecular Microbiology · doi:10.1111/mmi.13002 · Cited by 173
Role for Cell Density in Antifungal Drug Resistance in Candida albicans Biofilms
Perumal, P., Mekala, S., & Chaffin, W. L. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01237-06 · Cited by 165
Time Course Global Gene Expression Analysis of an In Vivo Candida Biofilm
Nett, J. E., Lepak, A. J., Marchillo, K., & Andes, D. R. (2009) · The Journal of Infectious Diseases · doi:10.1086/599838 · Cited by 162
Candida albicans: A Model Organism for Studying Fungal Pathogens
Kabir, M. A., Hussain, M. A., & Ahmad, Z. (2012) · ISRN Microbiology · doi:10.5402/2012/538694 · Cited by 170
Bonhomme, J., Chauvel, M., Goyard, S., Roux, P., Rossignol, T., & d'Enfert, C. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2011.07626.x · Cited by 144
The characteristics of Aspergillus fumigatus mycetoma development: is this a biofilm?
Mowat, E., Williams, C., Jones, B., Mcchlery, S., & Ramage, G. (2009) · Medical Mycology · doi:10.1080/13693780802238834 · Cited by 131
Self-citationPierce, C. G., Chaturvedi, A. K., Lazzell, A. L., Powell, A. T., Saville, S. P., McHardy, S. F., & Lopez-Ribot, J. L. (2015) · npj Biofilms and Microbiomes · doi:10.1038/npjbiofilms.2015.12 · Cited by 124
Candida albicans biofilms: building a heterogeneous, drug-tolerant environment
Bonhomme, J., & d’Enfert, C. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.03.007 · Cited by 120
Fox, E. P., & Nobile, C. J. (2012) · Transcription · doi:10.4161/trns.22281 · Cited by 114
The Transcriptional Regulator Nrg1p Controls Candida albicans Biofilm Formation and Dispersion
Uppuluri, P., Pierce, C. G., Thomas, D. P., Bubeck, S. S., Saville, S. P., & Lopez-Ribot, J. L. (2010) · Eukaryotic Cell · doi:10.1128/ec.00111-10 · Cited by 110
Dwivedi, P., Thompson, A., Xie, Z., Kashleva, H., Ganguly, S., Mitchell, A. P., & Dongari-Bagtzoglou, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016218 · Cited by 110
Divergent Approaches to Virulence in C. albicans and C. glabrata: Two Sides of the Same Coin
Galocha, M., Pais, P., Cavalheiro, M., Pereira, D., Viana, R., & Teixeira, M. C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092345 · Cited by 105
Candida albicans biofilm formation is associated with increased anti‐oxidative capacities
Seneviratne, C. J., Wang, Y., Jin, L., Abiko, Y., & Samaranayake, L. P. (2008) · PROTEOMICS · doi:10.1002/pmic.200701097 · Cited by 104
Biofilm Formation by Pneumocystis spp
Cushion, M. T., Collins, M. S., & Linke, M. J. (2009) · Eukaryotic Cell · doi:10.1128/ec.00202-08 · Cited by 96
Prostaglandin production during growth of Candida albicans biofilms
Alem, M. A., & Douglas, L. J. (2005) · Journal of Medical Microbiology · doi:10.1099/jmm.0.46172-0 · Cited by 91
Evasion of Immune Surveillance in Low Oxygen Environments Enhances Candida albicans Virulence
Lopes, J. P., Stylianou, M., Backman, E., Holmberg, S., Jass, J., Claesson, R., & Urban, C. F. (2018) · mBio · doi:10.1128/mbio.02120-18 · Cited by 88
Pseudomonas aeruginosa secreted factors impair biofilm development in Candida albicans
Holcombe, L. J., McAlester, G., Munro, C. A., Enjalbert, B., Brown, A. J. P., Gow, N. A. R., Ding, C., Butler, G., O'Gara, F., & Morrissey, J. P. (2010) · Microbiology · doi:10.1099/mic.0.037549-0 · Cited by 82
Lu, Y., Su, C., Mao, X., Raniga, P. P., Liu, H., & Chen, J. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-02-0173 · Cited by 82
Fungal MorphogenesisPreprint
Lin, X., Alspaugh, J. A., Liu, H., & Harris, S. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019679 · Cited by 86
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Dutton, L. C., Nobbs, A. H., Jepson, K., Jepson, M. A., Vickerman, M. M., Aqeel Alawfi, S., Munro, C. A., Lamont, R. J., & Jenkinson, H. F. (2014) · mBio · doi:10.1128/mbio.00911-14 · Cited by 75
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Ramage, G., Kean, R., Rautemaa-Richardson, R., Williams, C., & Lopez-Ribot, J. L. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-025-01147-0 · Cited by 72
Self-citationPurschke, F. G., Hiller, E., Trick, I., & Rupp, S. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.017673 · Cited by 60
Serrano‐Fujarte, I., López-Romero, E., Reyna-López, G. E., Martínez-Gámez, M. A., Vega‐González, A., & Cuéllar‐Cruz, M. (2015) · BioMed Research International · doi:10.1155/2015/783639 · Cited by 62
Cabral, V., Znaidi, S., Walker, L. A., Martin-Yken, H., Dague, E., Legrand, M., Lee, K., Chauvel, M., Firon, A., Rossignol, T., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004542 · Cited by 59
Brown, A. O., Graham, C. E., Cruz, M. R., Singh, K. V., Murray, B. E., Lorenz, M. C., & Garsin, D. A. (2019) · mBio · doi:10.1128/mbio.01334-19 · Cited by 46
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Gutiérrez-Correa, M., & Villena, G. K. (2003) · Revista Peruana de Biología · doi:10.15381/rpb.v10i2.2492 · Cited by 46
Ras signalling in pathogenic yeasts
Pentland, D. R., Piper-Brown, E., Mühlschlegel, F. A., & Gourlay, C. W. (2018) · Microbial Cell · doi:10.15698/mic2018.02.612 · Cited by 36
Kılıç, K., Koç, A. N., Tekinsen, F. F., Yildiz, P., Kılıç, D., Zararsız, G., & Kılıç, E. (2012) · Journal of Oral Implantology · doi:10.1563/aaid-joi-d-12-00048 · Cited by 37
Pentland, D. R., Davis, J., Mühlschlegel, F. A., & Gourlay, C. W. (2021) · npj Biofilms and Microbiomes · doi:10.1038/s41522-021-00238-z · Cited by 28
Lee, Y., Fang, Y., Sun, Y., Hsu, H., Weng, S., Tseng, T., Lin, T., & Shieh, J. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3930 · Cited by 16
Schena, N. C., Baker, K. M., Stark, A. A., Thomas, D. P., & Cleary, I. A. (2023) · PLOS ONE · doi:10.1371/journal.pone.0286547 · Cited by 15
Candida albicans Biofilms, Heterogeneity and Antifungal Drug Tolerance
LaFleur, M. D. (2011) · The Open Mycology Journal · doi:10.2174/1874437001105010021 · Cited by 6
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Vellanki, S., Huh, E. Y., Saville, S. P., & Lee, S. C. (2019) · Preprints.org · doi:10.20944/preprints201902.0025.v1 · Cited by 4
Schena, N. C., Baker, K. M., Stark, A. A., Thomas, D. P., & Cleary, I. A. (2026) · Folia Microbiologica · doi:10.1007/s12223-025-01288-y · Cited by 1
Biofilm: Structure, Antifungal Resistance, Proteomics and Genomics of Candida Species
Lotfali, E. (2019) · Open Access Journal of Mycology & Mycological Sciences · doi:10.23880/oajmms-16000108
Miyazima, T. Y. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.23.2014.tde-11092014-172928
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Tóth, R. (2016) · SZTE Repository of Dissertations (University of Szeged) · doi:10.14232/phd.3187
Hope, W. W. (2008) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1122869.580934
Sundstrom, P. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735327709.793564432
Munro, C. A. (2006) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.1032148.372802
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Metadata
- Authors
- Ramage, G., VandeWalle, K., López-Ribot, J. L., & Wickes, B. L.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Wickes, Brian L
- Venue
- FEMS Microbiology Letters
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-08
- Volume
- 214
- Issue
- 1
- Pages
- 95-100
- ISSN
- 0378-1097 (ISSN-L)
- 1574-6968
- OpenAlex
- W1981442035
- Cited by
- 334
- References
- 30
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 15 · 2023: 13 · 2022: 14 · 2021: 21 · 2020: 12 · 2019: 23 · 2018: 11 · 2017: 14 · 2016: 20 · 2015: 25 · 2014: 26 · 2013: 12 · 2012: 17
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEMS Microbiology Letters (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Candida albicans, biofilm formation, hyphal development, antifungal resistance, fluconazole resistance, amphotericin B resistance, Cph1, yeast-to-hypha transition
- MeSH terms
- Amphotericin B, Antifungal Agents, Candida albicans, Culture Media, DNA-Binding Proteins, Fungal Proteins, Microbial Sensitivity Tests, Microscopy, Electron, Scanning, Transcription Factors, Fluconazole, Gene Expression Regulation, Fungal, Biofilms
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