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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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Gonçalves, B., Bernardo, R., Wang, C., Schröder, M., Pedro, N. A., Butler, G., Azeredo, J., Henriques, M., Mira, N. P., & Silva, S. M. (2020) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2020.151414 · Cited by 16
Fidel, P. L., Yano, J., Esher, S. K., & Noverr, M. C. (2020) · Journal of Fungi · doi:10.3390/jof6010035 · Cited by 18
“albicans biofilm growth on vaginal epithelium has been suggested from animal studies [28], although the clinical significance of biofilms in VVC remains unknown [170].”
BackgroundResultInfluentialSelf-citationUnderstanding Vulvovaginal Candidiasis Through a Community Genomics Approach
Bradford, L. L., Ravel, J., & Bruno, V. M. (2013) · Current Fungal Infection Reports · doi:10.1007/s12281-013-0135-0 · Cited by 15
“One such approach is the investigation of Candida biofilm formation, which may provide increased adherence to the mucosa and resistance to antimycotic agents [25, 26].”
BackgroundThe Role of Biofilms in Contact Lens Associated Fungal Keratitis
Yi, J., Sun, Y., Zeng, C., Kostoulias, X., & Qu, Y. (2023) · Antibiotics · doi:10.3390/antibiotics12101533 · Cited by 14
Yano, J., & Fidel, P. L. (2024) · Infection and Immunity · doi:10.1128/iai.00350-23 · Cited by 15
“…visual examination of vaginal tissues from inoculated CVVC-S and CVVC-R mice via SEM, the former exhibiting fungal biofilm growth on the vaginal epithelium in line with previous reports (44), while the latter showed NETs in direct contact with C. albicans hyphae and minimal evidence of biofilms.”
ResultSelf-citationCharacterization of a Lactobacillus gasseri strain as a probiotic for female vaginitis
Zhang, J., Li, K., Cao, T., & Duan, Z. (2024) · Scientific Reports · doi:10.1038/s41598-024-65550-y · Cited by 15
Candida Infections in Immunocompetent Hosts: Pathogenesis and Diagnosis
Rudramurthy, S. M., & Singh, S. (2020) · Current Fungal Infection Reports · doi:10.1007/s12281-020-00392-5 · Cited by 16
Ganan, M., Lorentzen, S. B., Gaustad, P., & Sørlie, M. (2021) · Journal of Fungi · doi:10.3390/jof7090718 · Cited by 14
“Additionally, Candida biofilms have also been related to topical infections such as vaginal candidiasis [8,9] and oral candidiasis [10].”
BackgroundGonçalves, B., Azevedo, N. F., Henriques, M., & Silva, S. M. (2019) · Medical Mycology · doi:10.1093/mmy/myz070 · Cited by 17
Nikoomanesh, F., Roudbarmohammadi, S., Roudbary, M., Bayat, M., & Heidari, G. (2016) · Infection Epidemiology and Medicine · doi:10.18869/modares.iem.2.1.22 · Cited by 14
Candida palmioleophila: A New Emerging Threat in Brazil?
da Costa, G. L., Negri, M., de Miranda, R. P. R., Corrêa-Moreira, D., Pinto, T. C. A., Ramos, L. S., Ferreira, D. G., Salomão, B., Fumian, T. M., Mannarino, C. F., et al. (2023) · Journal of Fungi · doi:10.3390/jof9070770 · Cited by 14
Ranđelović, M., Dimitrijević, M., Otašević, S., Stanojevic, L. P., Išljamović, M., Ignjatović, A., Arsić-Arsenijević, V. S., & Stojanović-Radić, Z. Z. (2023) · Journal of Fungi · doi:10.3390/jof9111080 · Cited by 14
“Various investigations have been conducted to characterize biofilm formation, pathogenicity, and antifungal susceptibility profiles in clinical isolates from VVC and RVVC patients [16–18].”
BackgroundA confocal microscopy based method to monitor extracellular pH in fungal biofilms
Schlafer, S., Kamp, A., & Garcia, J. E. (2018) · FEMS Yeast Research · doi:10.1093/femsyr/foy049 · Cited by 13
Host Pathogen Relations: Exploring Animal Models for Fungal Pathogens
Harwood, C. A., & Rao, R. P. (2014) · Pathogens · doi:10.3390/pathogens3030549 · Cited by 13
“Excised murine vaginal mucosal tissue is also used as a substrate to study vaginal infections [61].”
BackgroundEdwards, J. E. (2015) · Elsevier eBooks · doi:10.1016/b978-1-4557-4801-3.00258-7 · Cited by 12
Caetano, C. F., Gaspar, C., Oliveira, A. S., Palmeira‐de‐Oliveira, R., Rodrigues, L., Gonçalves, T., Martinez‐de‐Oliveira, J., Palmeira‐de‐Oliveira, A., & Rolo, J. (2023) · Microorganisms · doi:10.3390/microorganisms11102398 · Cited by 12
“…and their virulence hand, can be and multiply factors. other hand grow and their virulence other hand grow and their virulence hand, can be and multiply factors. other hand, grow and virulence hand, can be and multiply factors. other hand grow and virulence effect on the , can be with C. albicans”
BackgroundNovel Strategies Against Candida Biofilms: Interest of Synthetic Compounds
Girardot, M., & Imbert, C. (2015) · Future Microbiology · doi:10.2217/fmb.15.118 · Cited by 12
Revealing Candida glabrata biofilm matrix proteome: global characterization and pH response
Gonçalves, B., Azevedo, N. F., Osório, H., Henriques, M., & Silva, S. M. (2021) · Biochemical Journal · doi:10.1042/bcj20200844 · Cited by 12
Anticandidal Activity of Omiganan and Its Retro Analog Alone and in Combination with Fluconazole
Czechowicz, P., Jaśkiewicz, M., Neubauer, D., Gościniak, G., & Kamysz, W. (2021) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-021-09757-9 · Cited by 11
“This fact may provide an argument to the hypothesis that the formation of a highly resistant and impermeable biofilm on the vaginal mucosa by Candida species is responsible for the lack of therapeutic effect of using azoles [2, 5, 7, 8, 10, 40, 41].”
BackgroundFernandes, L., Gonçalves, B., Costa, R. H. S., Fernandes, Â., Gomes, A., Nogueira‐Silva, C., Silva, S. M., Rodrigues, M. E., & Henriques, M. (2022) · Healthcare · doi:10.3390/healthcare10091649 · Cited by 11
“Furthermore, the vaginal pathogenicity of Candida organisms is facilitated by several virulence factors including the biofilm formation on vaginal walls and intrauterine devices (IUDs) [8].”
BackgroundCzechowicz, P., Neubauer, D., Nowicka, J., Kamysz, W., & Gościniak, G. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13101589 · Cited by 11
Virulence Factors as Promoters of Chronic Vulvovaginal Candidosis: A Review
Faria-Gonçalves, P., Rolo, J., Gaspar, C., Palmeira‐de‐Oliveira, R., Martinez‐de‐Oliveira, J., & Palmeira‐de‐Oliveira, A. (2021) · Mycopathologia · doi:10.1007/s11046-021-00592-8 · Cited by 10
Manohar, J., Hatt, S., DeMarzo, B. B., Blostein, F., Cronenwett, A. E. W., Wu, J., Lee, K. H., & Foxman, B. (2019) · American Journal of Infection Control · doi:10.1016/j.ajic.2019.08.005 · Cited by 10
Esposito, E., Campolo, M., Casili, G., Lanza, M., Filippone, A., Peritore, A. F., & Cuzzocrea, S. (2018) · Future Microbiology · doi:10.2217/fmb-2018-0102 · Cited by 10
Vaishnavi, K., Safar, L., & Devi, K. (2019) · Journal of Skin and Sexually Transmitted Diseases · doi:10.25259/jsstd_14_2019 · Cited by 10
Al-Madboly, L. A., El-Salam, M. A. A., Bastos, J. K., El-Shorbagy, S. H., & El-Morsi, R. M. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.02724-21 · Cited by 12
Original Research Article (Experimental)
Mudiar, R., & Kelkar-Mane, V. (2018) · Journal of Ayurveda and Integrative Medicine · doi:10.1016/j.jaim.2018.02.134 · Cited by 10
“As Candida can easily colonise on biotic and abiotic surfaces by biofilm formation [16], Tamrajal in comparison with standard antifungals as well as CuO NPs was investigated for its possible effects on biofilm.”
BackgroundWang, Y., Wang, Z., Li, Q., Feng, Y., Li, J., Lu, Y., Zhang, J., & Ke, X. (2025) · Journal of Controlled Release · doi:10.1016/j.jconrel.2025.113666 · Cited by 9
Revankar, S. G., & Sobel, J. D. (2014) · ASM Press eBooks · doi:10.1128/9781555817176.ch26 · Cited by 10
Czechowicz, P., Nowicka, J., Neubauer, D., Chodaczek, G., Krzyżek, P., & Gościniak, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214453 · Cited by 8
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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