The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Candida albicans forms biofilms on the vaginal mucosa
Open accessAbstract
Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges existing paradigms of host defence against fungal infection. While abiotic biofilm formation has a clearly established role during systemic Candida infections, it is not known whether C. albicans forms biofilms on the vaginal mucosa and the possible role of biofilms in disease. In vivo and ex vivo murine vaginitis models were employed to examine biofilm formation by scanning electron and confocal microscopy. C. albicans strains included 3153A (lab strain), DAY185 (parental control strain), and mutants defective in morphogenesis and/or biofilm formation in vitro (efg1/efg1 and bcr1/bcr1). Both 3153A and DAY815 formed biofilms on the vaginal mucosa in vivo and ex vivo as indicated by high fungal burden and microscopic analysis demonstrating typical biofilm architecture and presence of extracellular matrix (ECM) co-localized with the presence of fungi. In contrast, efg1/efg1 and bcr1/bcr1 mutant strains exhibited weak or no biofilm formation/ECM production in both models compared to wild-type strains and complemented mutants despite comparable colonization levels. These data show for the first time that C. albicans forms biofilms in vivo on vaginal epithelium, and that in vivo biotic biofilm formation requires regulators of biofilm formation (BCR1) and morphogenesis (EFG1).
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“Vaginal mucosal mouse models, both in vivo (live mice inoculated with C. albicans on the vaginal mucosa) and ex vivo (vaginas excised from euthanized mice and then inoculated with C. albicans in tissue culture plates), show similar biofilm architectures, with clear yeast, hyphae, and extracellular matrix evident throughout the biofilms formed on top of the mucosal layers (72).”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [72]
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Citations
Cites
Nonfilamentous C. albicans Mutants Are Avirulent
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“Second, in vivo vaginal tissue 3640 Microbiology 156 contains many secretions, composed of electrolytes, organic acids and proteins, which maintain properties such as pH and osmolarity (Owen & Katz, 1999).”
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“Our results are also consistent with the kinetics of in vitro biofilms grown on silicone discs, which show steady increases in dry weight measurements until 36–48 h and then remain stationary (Chandra et al., 2001; Hawser & Douglas, 1994).”
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 · cited 1×
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BackgroundCandida 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 · cited 1×
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How to build a biofilm: a fungal perspective
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Critical Role of Bcr1-Dependent Adhesins in C. albicans Biofilm Formation In Vitro and In Vivo
Nobile, C. J., Andes, D. R., Nett, J. E., Smith, F. J., Yue, F., Phan, Q.-T., Edwards, J. E., Filler, S. G., & Mitchell, A. P. (2006) · PLoS Pathogens · doi:10.1371/journal.ppat.0020063 · Cited by 507 · cited 6×
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InfluentialRegulation 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
Putative Role of β-1,3 Glucans in Candida albicans Biofilm Resistance
Nett, J., Lincoln, L., Marchillo, K., Massey, R., Holoyda, K., Hoff, B., VanHandel, M., & Andes, D. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01056-06 · Cited by 407 · cited 1×
“ConA is a lectin that binds to C. albicans polysaccharides secreted as part of the matrix. b-Glucan is a cell wall polysaccharide that has been detected in Candida ECM by a Limulus amoebocyte lysate clotting enzyme based assay (Nett et al., 2007a, b).”
MethodHigh-Frequency Switching of Colony Morphology in Candida albicans
Slutsky, B., Buffo, J., & Soll, D. R. (1985) · Science · doi:10.1126/science.3901258 · Cited by 400 · cited 1×
“3153A Wild-type Slutsky et al. (1985)”
Function of Candida albicans Adhesin Hwp1 in Biofilm Formation
Nobile, C. J., Nett, J. E., Andes, D. R., & Mitchell, A. P. (2006) · Eukaryotic Cell · doi:10.1128/ec.00194-06 · Cited by 395 · cited 7×
“…biofilm formation, i.e. ECM production and hyphal growth. http://mic.sgmjournals.org 3641 BCR1 encodes a transcriptional regulator that is required for production of vigorous biofilms on abiotic surfaces in vitro and in vivo in a catheter model (Nobile et al., 2006a; Nobile & Mitchell, 2005).”
InfluentialBaillie, G. S. (2000) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/46.3.397 · Cited by 389 · cited 2×
“These data show for the first time that C. albicans forms biofilms in vivo on vaginal epithelium, and that in vivo biotic biofilm formation requires regulators of biofilm formation (BCR1) and morphogenesis (EFG1).”
Characteristics of biofilm formation by Candida albicans.
Ramage, G., VandeWalle, K., Wickes, B. L., & Lopez-Ribot, J. L. (2001) · PubMed · Cited by 370
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“Prior to this study, the only in vivo vaginal biofilm characterized was bacterial, consisting of Gardnerella vaginalis (Scott et al., 1989; Swidsinski et al., 2008; van der Meijden et al., 1988).”
Ramage, G., VandeWalle, K., López-Ribot, J. L., & Wickes, B. L. (2002) · FEMS Microbiology Letters · doi:10.1016/s0378-1097(02)00853-4 · Cited by 334 · cited 4×
“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).”
InfluentialPathogenesis and Treatment of Recurrent Vulvovaginal Candidiasis
Sobel, J. D. (1992) · Clinical Infectious Diseases · doi:10.1093/clinids/14.supplement_1.s148 · Cited by 277 · cited 2×
“%) experience recurrent vulvovaginal candidiasis (RVVC), defined as having three or more episodes per year (Sobel, 1992).”
BackgroundCandida albicans RIM101 pH Response Pathway Is Required for Host-Pathogen Interactions
Davis, D. A., Edwards, J. E., Mitchell, A. P., & Ibrahim, A. S. (2000) · Infection and Immunity · doi:10.1128/iai.68.10.5953-5959.2000 · Cited by 276
Fidel, P. L., Barousse, M. M., Espinosa, T., Ficarra, M., Sturtevant, J. E., Martin, D. H., Quayle, A. J., & Dunlap, K. (2004) · Infection and Immunity · doi:10.1128/iai.72.5.2939-2946.2004 · Cited by 258 · cited 2×
“In resistant women, vaginal epithelial cells are important for protection against infection (Fidel et al., 2004).”
Self-citationIntravascular Catheter-Associated Infections
Crump, J. A., & Collignon, P. (2000) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s100960050001 · Cited by 252 · cited 1×
“Significant attention has been given to Candida biofilm formation of indwelling catheters, which can lead to life-threatening systemic infections (Crump & Collignon, 2000; Dominic et al., 2007; Kojic & Darouiche, 2004).”
BackgroundCharacterization of Mucosal Candida albicans Biofilms
Dongari‐Bagtzoglou, A. I., Kashleva, H., Dwivedi, P., Diaz, P. I., & Vasilakos, J. P. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007967 · Cited by 214 · cited 4×
“albicans was shown to form biofilms on oral mucosa in an immunosuppressed murine model of oropharyngeal candidiasis (Dongari-Bagtzoglou et al., 2009).”
InfluentialPrevalence of vulvovaginal candidiasis and susceptibility to fluconazole in women
Bauters, T. G. M., Dhont, M. A., Temmerman, M., & Nelis, H. J. C. F. (2002) · American Journal of Obstetrics and Gynecology · doi:10.1067/mob.2002.125897 · Cited by 174
Animal models of mucosal Candida infection
Naglik, J. R., Fidel, P. L., & Odds, F. C. (2008) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2008.01160.x · Cited by 173 · cited 1×
“Higher inocula were used for DAY185 and mutants because initial experiments demonstrated that 3153A colonizes mucosal tissue better than DAY185 and biofilm mutants, as previously reported (Naglik et al., 2008; Taylor et al., 2000).”
Self-citationRequirement for Candida albicans Sun41 in Biofilm Formation and Virulence
Norice, C. T., Smith, F. J., Solis, N. V., Filler, S. G., & Mitchell, A. P. (2007) · Eukaryotic Cell · doi:10.1128/ec.00314-07 · Cited by 122 · cited 1×
“arg4 : : hisG Norice et al. (2007)”
β‐1,3 Glucan as a Test for Central Venous Catheter Biofilm Infection
Nett, J. E., Lincoln, L. M., Marchillo, K., & Andes, D. R. (2007) · The Journal of Infectious Diseases · doi:10.1086/517522 · Cited by 94 · cited 1×
“ConA is a lectin that binds to C. albicans polysaccharides secreted as part of the matrix. b-Glucan is a cell wall polysaccharide that has been detected in Candida ECM by a Limulus amoebocyte lysate clotting enzyme based assay (Nett et al., 2007a, b).”
MethodGrowth Inhibition ofCandida albicansby Human Vaginal Epithelial Cells
Barousse, M. M., Steele, C. H., Dunlap, K., Espinosa, T., Boikov, D. A., Sobel, J. D., & Fidel, P. L. (2001) · The Journal of Infectious Diseases · doi:10.1086/324532 · Cited by 82 · cited 2×
“C. albicans strains included 3153A (lab strain), DAY185 (parental control strain), and mutants defective in morphogenesis and/or biofilm formation in vitro (efg1/ efg1 and bcr1/bcr1).”
Self-citationMathema, B., Cross, E., Dun, E., Park, S., Bedell, J., Slade, B., Williams, M., Riley, L., Chaturvedi, V., & Perlin, D. S. (2001) · Clinical Infectious Diseases · doi:10.1086/322600 · Cited by 65 · cited 1×
“Finally, with C. albicans rarely exhibiting resistance to azoles during VVC (Bauters et al., 2002; Mathema et al., 2001), how does this relate to the high rates of biofilm resistance on abiotic surfaces?”
BackgroundBarousse, M. M., Espinosa, T., Dunlap, K., & Fidel, P. L. (2005) · Infection and Immunity · doi:10.1128/iai.73.11.7765-7767.2005 · Cited by 55
Self-citationEffect of filamentation and mode of growth on antifungal susceptibility of Candida albicans
Watamoto, T., Samaranayake, L. P., Jayatilake, J. A. M. S., Egusa, H., Yatani, H., & Seneviratne, C. J. (2009) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2009.03.008 · Cited by 53 · cited 1×
“Accordingly, the efg1/efg1 mutant is unable to form biofilms in vitro in RPMI or YNB+glucose; however, its biofilm formation ability in vivo has not been previously reported (Ramage et al., 2002; Watamoto et al., 2009).”
Candida biofilms in medical devices: evolving trends.
Dominic, R. M. S., Shenoy, S. M., & Baliga, S. (2007) · PubMed · Cited by 45
Taylor, B. N., Fichtenbaum, C. J., Saavedra, M. C., Slavinsky, J., Swoboda, R., Wozniak, K. L., Arribas, A. R., Powderly, W. G., & Fidel, P. L. (2000) · The Journal of Infectious Diseases · doi:10.1086/315768 · Cited by 37 · cited 1×
“Higher inocula were used for DAY185 and mutants because initial experiments demonstrated that 3153A colonizes mucosal tissue better than DAY185 and biofilm mutants, as previously reported (Naglik et al., 2008; Taylor et al., 2000).”
Self-citationScott, T. G., Curran, B., & Smyth, C. J. (1989) · Microbiology · doi:10.1099/00221287-135-3-475 · Cited by 32 · cited 1×
“Prior to this study, the only in vivo vaginal biofilm characterized was bacterial, consisting of Gardnerella vaginalis (Scott et al., 1989; Swidsinski et al., 2008; van der Meijden et al., 1988).”
Descriptive Light and Electron Microscopy of Normal and Clue-Cell-Positive Discharge
van der Meijden, W. I., Koerten, H. K., van Mourik, W., & de Bruijn, W. C. (2010) · Gynecologic and Obstetric Investigation · doi:10.1159/000293745 · Cited by 12 · cited 1×
“Prior to this study, the only in vivo vaginal biofilm characterized was bacterial, consisting of Gardnerella vaginalis (Scott et al., 1989; Swidsinski et al., 2008; van der Meijden et al., 1988).”
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Sardi, J. C. O., Scorzoni, L., Bernardi, T., Fusco-Almeida, A. M., & Mendes Giannini, M. J. S. (2013) · Journal of Medical Microbiology · doi:10.1099/jmm.0.045054-0 · Cited by 1,184
“Most infections result from pathogenic biofilms; therefore, the biomedical significance of biofilms is substantial (Ganguly & Mitchell, 2011; Harriott et al., 2010).”
BackgroundCandida 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
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“albicans in 166 tissue culture plates) also show similar biofilm architectures with yeast cells, hyphae, 167 and extracellular matrix evident throughout the biofilms, formed on top of mucosal 168 layers [18].”
BackgroundResistance of Candida to azoles and echinocandins worldwide
Pristov, K. E., & Ghannoum, M. A. (2019) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2019.03.028 · Cited by 706
“Biofilms allow the cells to adhere to and proliferate onmedically implanted devices as well as host tissue, causing infections [10,18,19].”
BackgroundGenetic control of Candida albicans biofilm development
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“albicans produces dense three-dimensional biofilms that are embedded in extracellular matrix materia”
Metadata
- Authors
- Harriott, M. M., Lilly, E. A., Rodriguez, T. E., Fidel, P. L., & Noverr, M. C.
- Affiliations
- Wayne State University (US)
- Louisiana State University Health Sciences Center New Orleans (US)
- Venue
- Microbiology
- Publisher
- Microbiology Society
- Published
- 2010-12-01
- Volume
- 156
- Issue
- 12
- Pages
- 3635-3644
- ISSN
- 1350-0872 (ISSN-L)
- 1465-2080
- PMC
- PMC3068702
- OpenAlex
- W2063801124
- Cited by
- 301
- References
- 35
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 13 · 2023: 20 · 2022: 19 · 2021: 26 · 2020: 27 · 2019: 24 · 2018: 16 · 2017: 25 · 2016: 21 · 2015: 26 · 2014: 25 · 2013: 16 · 2012: 9
- FWCI
- 7.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Microbiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Louisiana Board of Regents
- Carnegie Mellon University
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01 AI72406-01, R01AI072406, R01AI32556, R01AI032556)
- 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, vaginal mucosa, vaginal candidiasis, vaginal epithelium, extracellular matrix, BCR1, EFG1, morphogenesis, fungal virulence
- MeSH terms
- Animals, Candida albicans, Candidiasis, Female, Humans, Mice, Inbred C57BL, Mucous Membrane, Vagina, Biofilms, Dioxygenases, Mice
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