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Interface of Candida albicans Biofilm Matrix-Associated Drug Resistance and Cell Wall Integrity Regulation
Open accessAbstract
Candida albicans frequently infects medical devices by growing as a biofilm, i.e., a community of adherent organisms entrenched in an extracellular matrix. During biofilm growth, Candida spp. acquire the ability to resist high concentrations of antifungal drugs. One recently recognized biofilm resistance mechanism involves drug sequestration by matrix β-1,3 glucan. Using a candidate gene approach, we investigated potential C. albicans β-1,3-glucan regulators, based on their homology to Saccharomyces cerevisiae , including SMI1 and protein kinase C (PKC) pathway components. We identified a role for the SMI1 in biofilm matrix glucan production and development of the associated drug resistance phenotype. This pathway appears to act through transcription factor Rlmp and glucan synthase Fks1p. The phenotypes of these mutant biofilms mimicked those of the smi1 Δ/ smi1 Δ biofilm, and overexpression of FKS1 in the smi1 Δ/ smi1 Δ mutant restored the biofilm resistant phenotype. However, control of this pathway is distinct from that of the upstream PKC pathway because the pkc1 Δ/ pkc1 Δ, bck1 Δ/ bck1 Δ, mkk2 Δ/ mkk2 Δ, and mkc1 Δ/ mkc1 Δ biofilms retained the resistant phenotype of the parent strain. In addition, resistance to cell-perturbing agents and gene expression data do not support a significant role for the cell wall integrity pathway during the biofilm formation. Here we show that Smi1p functions in conjunction with Rlm1p and Fks1p to produce drug-sequestering biofilm β-glucan. Our work provides new insight into how the C. albicans biofilm matrix production and drug resistance pathways intersect with the planktonic cell wall integrity pathway. This novel connection helps explain how pathogens in a multicellular biofilm community are protected from anti-infective therapy.
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In the citing paper
“Two known transcriptional regulators of biofilm matrix production in C. albicans are Rlm1 and Zap1.”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [136]
In the citing paper
“Deletion of RLM1 causes a reduction in matrix levels (136), whereas deletion of ZAP1 leads to an increase in the accumulation of extracellular matrix material, probably by upregulating the glucoamylases Gca1 and Gca2 (144).”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [136]
In the citing paper
“The transcriptional regulator Rlm1 (discussed above) contributes to antifungal drug resistance by regulating the expression of FKS1 (136).”
From Candida albicans Biofilms and Human Disease (2015) · cites this paper as [136]
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Bacterial Biofilms: A Common Cause of Persistent Infections
Costerton, J. W., Stewart, P. S., & Greenberg, E. P. (1999) · Science · doi:10.1126/science.284.5418.1318 · Cited by 12,167
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Pappas, P. G., Kauffman, C. A., Andes, D., Benjamin, D. K., Calandra, T. F., Edwards, J. E., Filler, S. G., Fisher, J. F., Kullberg, B.-J., Zeichner, L. O., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/596757 · Cited by 3,191
Self-citationChandra, J., Kuhn, D. M., Mukherjee, P. K., Hoyer, L. L., McCormick, T., & Ghannoum, M. A. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.18.5385-5394.2001 · Cited by 1,578
A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance
Mah, T., Pitts, B., Pellock, B. J., Walker, G. C., Stewart, P. S., & O’Toole, G. A. (2003) · Nature · doi:10.1038/nature02122 · Cited by 1,190
Candida Infections of Medical Devices
Kojic, E. M., & Darouiche, R. O. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.2.255-267.2004 · Cited by 1,055
Sanglard, D., Kuchler, K., Ischer, F., Pagani, J. L., Monod, M., & Bille, J. (1995) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.39.11.2378 · Cited by 815
Rapid Hypothesis Testing with Candida albicans through Gene Disruption with Short Homology Regions
Wilson, R. B., Davis, D. A., & Mitchell, A. P. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.6.1868-1874.1999 · Cited by 763
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
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Longo, L. V. G., Goodyear, E. G., Zhang, S., Kudryashova, E., & Wu, J. (2021) · Molecular Biology of the Cell · doi:10.1091/mbc.e21-04-0214 · Cited by 15
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Zhang, Q., Yang, N., Mao, R., Hao, Y., Ma, X., Teng, D., Fan, H., & Wang, J. (2021) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-021-11135-y · Cited by 15
Wang, Y., Huang, S.-H., Lan, C., & Chen, B.-S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035339 · Cited by 16
Tanaka, Y., Sasaki, M., Ito, F., Aoyama, T., Okamoto, M., Takahashi‐Nakaguchi, A., Chibana, H., & Shibata, N. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161371 · Cited by 14
Cong, L., Liao, Y., Yang, S., & Yang, R. (2017) · Mycopathologia · doi:10.1007/s11046-017-0119-7 · Cited by 14
Tanaka, Y., Sasaki, M., Ito, F., Aoyama, T., Sato-Okamoto, M., Takahashi-Nakaguchi, A., Chibana, H., & Shibata, N. (2018) · Fungal Biology · doi:10.1016/j.funbio.2017.09.007 · Cited by 13
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Kumar, D., & Kumar, A. (2023) · Microbial Drug Resistance · doi:10.1089/mdr.2022.0347 · Cited by 11
Wang, Y., Cui, X., Xiao, J., Kang, X., Hu, J., Huang, Z., Li, N., Yang, C., Pan, Y., & Zhang, S. (2024) · Molecular Plant Pathology · doi:10.1111/mpp.13493 · Cited by 12
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Priya, A., & Pandian, S. K. (2022) · Medical Mycology · doi:10.1093/mmy/myac039 · Cited by 11
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Wang, W., Lai, T.-X., Wu, Y., Chen, Z.-T., Tseng, K., & Lan, C. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.03285-22 · Cited by 11
Martin‐Yken, H., Bedekovic, T., Brand, A., Richard, M. L., Znaidi, S., d’Enfert, C., & Dague, É. (2018) · The Cell Surface · doi:10.1016/j.tcsw.2018.10.002 · Cited by 10
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Shepardson, K. M., & Cramer, R. A. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.03.003 · Cited by 11
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Costa, A. C. B. P., Omran, R. P., Correia‐Mesquita, T. O., Dumeaux, V., & Whiteway, M. S. (2019) · Scientific Reports · doi:10.1038/s41598-019-45624-y · Cited by 9
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Perlin, D. S. (2015) · ASM Press eBooks · doi:10.1128/9781555817381.ch130 · Cited by 7
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Vogel, M., Köberle, M., Schäffler, H., Treiber, M. K., Autenrieth, I. B., & Schumacher, U. (2013) · F1000Research · doi:10.12688/f1000research.2-106.v1 · Cited by 7
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Tuan, D. A., & Uyen, P. V. N. (2026) · Future Microbiology · doi:10.1080/17460913.2026.2678152 · Cited by 2
Achilonu, C. C. (2026) · Drugs and Drug Candidates · doi:10.3390/ddc5030047 · Cited by 2
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Self-citationSethi, K., Cortés, J. C. G., Sato, M., Osumi, M., Naqvi, N. I., Ribas, J. C., & Balasubramanian, M. K. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.05.23.493069 · Cited by 1
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Perlin, D. S. (2023) · ClinMicroNow · doi:10.1002/9781683674849.mcm0134 · Cited by 1
Mattiello, S. P. (2015) · Americanae (AECID Library)
Overcoming the antifungal drug resistance of biofilms on dental acrylic
Newsham-West, K. (2013) · Otago University Research Archive (University of Otago)
Pós-Graduação, P. D., Eduardo, C., & Teixeira, C. (2014)
Manfiolli, A. O., dos Reis, T. F., de Assis, L. J., de Castro, P. A., Silva, L. P., Hori, J. I., Walker, L. A., Munro, C. A., Rajendran, R., Ramage, G., et al. (2020) · The Cell Surface · doi:10.1016/j.tcsw.2020.100035
Le più antiche asce a margini rialzati della Sardegna
Schiavo, F. L. (1989) · Rivista di scienze preistoriche
(2021) · Elsevier eBooks · doi:10.1016/b978-0-12-816983-4.00003-1
Samanta, I., & Bandyopadhyay, S. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815770-1.00026-2
Sutar, Y. B., Nabeela, S., Singh, S., Alqarihi, A., Solis, N. V., Ghebremariam, T., Filler, S. G., Ibrahim, A. S., Date, A. A., & Uppuluri, P. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.02.494588
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Kim, M.-J., Żarnowski, R., & Andes, D. R. (2025) · Springer series on biofilms · doi:10.1007/978-3-031-93315-8_8
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Denega, I. (2020) · theses.fr (ABES) · doi:10.70675/748584ddzf6f4z4124z9237z56d0535d3352
Li, Y.-L., Liu, Q., Deng, Y.-M., Liu, J., Zhang, C., Huang, Z.-W., Zhou, B., Liang, Y., Lin, Q.-L., & Gong, Z. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.154500
Cristy, S. A., Walker, J. N., & Lorenz, M. C. (2026) · mBio · doi:10.1128/mbio.01785-26
Grossman, N. T., & Casadevall, A. (2026) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00915-26
Metadata
- Authors
- Nett, J. E., Sanchez, H., Cain, M. T., Ross, K. M., & Andes, D. R.
- Affiliations
- University of Wisconsin–Madison (US)
- Department of Medicine, University of Wisconsin, Madison, Wisconsin
- Corresponding author
- Andes, David R.
- Venue
- Eukaryotic Cell
- Publisher
- American Society for Microbiology
- Published
- 2011-12
- Volume
- 10
- Issue
- 12
- Pages
- 1660-1669
- ISSN
- 1535-9778 (ISSN-L)
- 1535-9786
- PMC
- PMC3232725
- OpenAlex
- W2138246367
- Cited by
- 168
- References
- 54
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 13 · 2021: 12 · 2020: 16 · 2019: 8 · 2018: 13 · 2017: 12 · 2016: 17 · 2015: 12 · 2014: 9 · 2013: 17 · 2012: 7
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Eukaryotic Cell (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL007899)
- National Institute of Allergy and Infectious Diseases (R01AI073289)
- 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, antifungal resistance, β-1,3-glucan, extracellular matrix, glucan synthase, protein kinase C pathway, cell wall integrity pathway, drug sequestration, medical device infections, biofilm formation
- MeSH terms
- Animals, Antifungal Agents, Candida albicans, Candidiasis, Cell Wall, Fungal Proteins, Glucosyltransferases, Protein Kinase C, Virulence, Fluconazole, Gene Expression Regulation, Fungal, Biofilms, Drug Resistance, Fungal, beta-Glucans, Mice, Rats, Gene Knockout Techniques, Catheters
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