Candida albicans strains deficient in CHS7, a key regulator of chitin synthase III, exhibit morphogenetic alterations and attenuated virulence
Abstract
Chitin is a structural polysaccharide present in most fungal cell walls, whose synthesis depends on a family of enzymic activities named chitin synthases (CSs). The specific role of each of them, as well as of their regulatory proteins, in cell morphogenesis and virulence is not well understood. Here, it is shown that most chitin synthesis in Candida albicans, one of the fungi most commonly isolated from opportunistic mycoses and infections, depends on CHS7. Thus,C. albicans chs7 Δ null mutants showed reduced levels of chitin and CS activity, and were resistant to Calcofluor. Despite the sequence similarity and functional relationship with ScChs7p, CaChs7p was unable to restore CSIII activity in a Saccharomyces cerevisiae chs7 Δ null mutant, because it was unable to direct ScChs3p export from the endoplasmic reticulum.C. albicans chs7 Δ null mutants did not show any defect in growth rate, but yeast cells displayed minor morphogenetic defects affecting septum formation, and showed an increased tendency to form filaments. CaChs7p was not required for germ-tube emission, and null mutant strains underwent the dimorphic transition correctly. However, colony morphology appeared distinctively affected.chs7 Δ hyphae were very curved and had irregular lateral walls, resulting in very compact colonies that seemed unable to spread out radially on the surface, unlike the wild-type. This growth pattern may be associated with the reduced virulence and high clearance rate observed when the chs7 Δ strain was used in a murine model of infection. Therefore, CaChs7p is required for normal hyphal morphogenesis, suggesting that in C. albicans CSIII plays an important role in maintaining cell wall integrity, being essential when invading surrounding tissues.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Chs3p is responsible for the deposition of the majority of chitin located in the lateral wall and chitin ring but not in the chitin disk of the primary septum.
“CW-staining, specific for chitin, was comparable to the wild type strain except for chs3Δ cells that were CW-positive only at the thin line of the septa, an observation in agreement with Chs3p being responsible for the deposition of the majority of chitin located in the lateral wall and chitin ring but not in the chitin disk of the primary septum [48, 49].”
From Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling (2016) · cites this paper as [48]
Cites
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 · see citing works
Virulence factors of Candida albicans
Calderone, R. A., & Fonzi, W. A. (2001) · Trends in Microbiology · doi:10.1016/s0966-842x(01)02094-7 · Cited by 1,331 · see citing works
Gillum, A. M., Tsay, E. Y. H., & Kirsch, D. R. (1984) · Molecular and General Genetics MGG · doi:10.1007/bf00328721 · Cited by 1,253 · see citing works
Mumberg, D., Müller, R., & Funk, M. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.25.5767 · Cited by 959 · see citing works
Lee, K. L., BUCKLEY, H. R., & Campbell, C. C. (1975) · Medical Mycology · doi:10.1080/00362177585190271 · Cited by 791 · see citing works
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 · see citing works
Cell Wall and Secreted Proteins of<i>Candida albicans</i>: Identification, Function, and Expression
Chaffin, W. L., López-Ribot, J. L., Casanova, M., Gozalbo, D., & Martínez, J. P. (1998) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.62.1.130-180.1998 · Cited by 726 · see citing works
The genetic complexity of chitin synthesis in fungi
Roncero, C. (2002) · Current Genetics · doi:10.1007/s00294-002-0318-7 · Cited by 328 · see citing works
Self-citationCIp10, an efficient and convenient integrating vector for Candida albicans
Murad, A. M. A., Lee, P. R., Broadbent, I. D., Barelle, C. J., & Brown, A. J. P. (2000) · Yeast · doi:10.1002/1097-0061(20000315)16:4 · Cited by 303 · see citing works
Regulatory networks controlling Candida albicans morphogenesis
Brown, A. J. P., & Gow, N. A. R. (1999) · Trends in Microbiology · doi:10.1016/s0966-842x(99)01556-5 · Cited by 301 · see citing works
Brand, A., MacCallum, D. M., Brown, A. J. P., Gow, N. A. R., & Odds, F. C. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.4.900-909.2004 · Cited by 272 · see citing works
Targeting of Chitin Synthase 3 to Polarized Growth Sites in Yeast Requires Chs5p and Myo2p
Santos, B., & Snyder, M. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.136.1.95 · Cited by 200 · see citing works
Differential regulation of cell wall biogenesis during growth and development in yeast
Smits, G. J., ENDE, H. V. D., & Klis, F. M. (2001) · Microbiology · doi:10.1099/00221287-147-4-781 · Cited by 191 · see citing works
Chitin synthesis in human pathogenic fungi
Munro, C. A., & Gow, N. A. R. (2001) · Medical Mycology · doi:10.1080/mmy.39.1.41.53 · Cited by 191 · see citing works
Septin Function in Candida albicans Morphogenesis
Warenda, A. J., & Konopka, J. B. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-01-0013 · Cited by 188 · see citing works
Chitin Synthesis in Candida albicans : Comparison of Yeast and Hyphal Forms
Braun, P. C., & Calderone, R. (1978) · Journal of Bacteriology · doi:10.1128/jb.133.3.1472-1477.1978 · Cited by 184 · see citing works
Navarro-García, F., Sánchez, M., Plá, J., & Nombela, C. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.4.2197 · Cited by 182 · see citing works
Virulence genes in the pathogenic yeastCandida albicans
Navarro-García, F., Sánchez, M., Nombela, C., & Plá, J. (2001) · FEMS Microbiology Reviews · doi:10.1111/j.1574-6976.2001.tb00577.x · Cited by 170 · see citing works
Munro, C. A., Winter, K., Buchan, A., Henry, K., Becker, J. M., Brown, A. J. P., Bulawa, C. E., & Gow, N. A. R. (2001) · Molecular Microbiology · doi:10.1046/j.1365-2958.2001.02347.x · Cited by 162 · see citing works
Trilla, J. A., Durán, Á., & Roncero, C. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.6.1153 · Cited by 156 · see citing works
Self-citationIsolation and characterization of Saccharomyces cerevisiae mutants resistant to Calcofluor white
Roncero, C., Valdivieso, M. ‐., Ribas, J. C., & Durán, A. (1988) · Journal of Bacteriology · doi:10.1128/jb.170.4.1950-1954.1988 · Cited by 153 · see citing works
Self-citationGaughran, J. P., LAI, M. H., Kirsch, D. R., & Silverman, S. J. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.18.5857-5860.1994 · Cited by 148 · see citing works
Attenuated virulence of chitin-deficient mutants of Candida albicans.
Bulawa, C. E., Miller, D. W., Henry, L. K., & Becker, J. M. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.23.10570 · Cited by 146 · see citing works
Gow, N. A., Robbins, P. W., Lester, J. W., Brown, A. J., Fonzi, W. A., Chapman, T., & Kinsman, O. S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.13.6216 · Cited by 145 · see citing works
Mattia, E. D., Carruba, G., Angiolella, L., & Cassone, A. (1982) · Journal of Bacteriology · doi:10.1128/jb.152.2.555-562.1982 · Cited by 133 · see citing works
Role of three chitin synthase genes in the growth of Candida albicans
Mio, T., Yabe, T., Sudoh, M., Satoh, Y., Nakajima, T., Arisawa, M., & Yamada-Okabe, H. (1996) · Journal of Bacteriology · doi:10.1128/jb.178.8.2416-2419.1996 · Cited by 124 · see citing works
Molecular organization of the cell wall of Candida albicans
Klis, F. M., De Groot, P., & Hellingwerf, K. (2001) · Medical Mycology · doi:10.1080/744118876 · Cited by 111 · see citing works
Growth Kinetics and Morphology of Colonies of the Filamentous Form of Candida albicans
Gow, N. A. R., & Gooday, G. W. (1982) · Microbiology · doi:10.1099/00221287-128-9-2187 · Cited by 105 · see citing works
Regulation of chitin synthesis during dimorphic growth of Candida albicans
Munro, C. A., Schofield, D. A., Gooday, G. W., & Gow, N. A. R. (1998) · Microbiology · doi:10.1099/00221287-144-2-391 · Cited by 101 · see citing works
Candida albicans Septin Mutants Are Defective for Invasive Growth and Virulence
Warenda, A. J., Kauffman, S., Sherrill, T. P., Becker, J. M., & Konopka, J. B. (2003) · Infection and Immunity · doi:10.1128/iai.71.7.4045-4051.2003 · Cited by 95 · see citing works
Munro, C. A., Whitton, R. K., Bleddyn Hughes, H., Rella, M., Selvaggini, S., & Gow, N. A. R. (2003) · Fungal Genetics and Biology · doi:10.1016/s1087-1845(03)00083-5 · Cited by 91 · see citing works
The Use of Divalent Cations and pH for the Determination of Specific Yeast Chitin Synthetases
Choi, W. J., & Cabib, E. (1994) · Analytical Biochemistry · doi:10.1006/abio.1994.1278 · Cited by 77 · see citing works
Zaragoza, Ó., VIRGILIO, C. D., Pontón, J., & Gancedo, C. (2002) · Microbiology · doi:10.1099/00221287-148-5-1281 · Cited by 65 · see citing works
Staib, P., Kretschmar, M., Nichterlein, T., Hof, H., & Morschhäuser, J. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02967.x · Cited by 58 · see citing works
Inhibitory effect of nikkomycin Z on chitin synthases in Candida albicans
Kim, M. K., Park, H., Kim, C. H., Park, H., & Choi, W. (2002) · Yeast · doi:10.1002/yea.837 · Cited by 58 · see citing works
Cell wall of pathogenic yeasts and implications for antimycotic therapy.
Cassone, A. (1986) · PubMed · Cited by 46 · see citing works
Sanz, M., Trilla, O. A., Duran, N., & Roncero, C. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02812.x · Cited by 41 · see citing works
Self-citationKrishnamurthy, S., Chatterjee, U., Gupta, V., Prasad, R., Das, P. K., Snehlata, P., Hasnain, S. E., & Prasad, R. (1998) · Yeast · doi:10.1002/(sici)1097-0061(19980430)14:6 · Cited by 38 · see citing works
Biochemistry and Molecular Biology
(2004) · Springer eBooks · doi:10.1007/978-3-662-06064-3 · Cited by 30 · see citing works
Sudoh, M., Tatsuno, K., Ono, N., Ohta, A., Chibana, H., Yamada‐Okabe, H., & Arisawa, M. (1999) · Microbiology · doi:10.1099/13500872-145-7-1613 · Cited by 26 · see citing works
Chitin Biosynthesis and Morphogenetic Processes
Valdivieso, M. ‐., Durán, Á., & Roncero, C. (2004) · Springer eBooks · doi:10.1007/978-3-662-06064-3_14 · Cited by 9 · see citing works
Self-citationThe Determination of Chitin Synthases by Varying pH and Divalent Cations in Candida albicans
Choi, W. (1998) · Journal of Microbiology and Biotechnology · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Banks, I. R., Specht, C. A., Donlin, M. J., Gerik, K. J., Levitz, S. M., & Lodge, J. K. (2005) · Eukaryotic Cell · doi:10.1128/ec.4.11.1902-1912.2005 · Cited by 245 · see citing works
Munro, C. A. (2013) · Advances in applied microbiology · doi:10.1016/b978-0-12-407678-5.00004-0 · Cited by 87 · see citing works
Participation of Candida albicans Transcription Factor RLM1 in Cell Wall Biogenesis and Virulence
Delgado-Silva, Y., Vaz, C., Carvalho-Pereira, J., Carneiro, C., Nogueira, E., Correia, A., Carreto, L. C., Silva, S. M., Faustino, A., Pais, C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086270 · Cited by 78 · see citing works
Yang, F., Kravets, A., Bethlendy, G., Welle, S., & Rustchenko, E. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00516-13 · Cited by 60 · see citing works
Protein profiling of the dimorphic, pathogenic fungus, Penicillium marneffei
Chandler, J. M., Treece, E. R., Trenary, H. R., Brenneman, J. L., Flickner, T. J., Frommelt, J. L., Oo, Z. M., Patterson, M. M., Rundle, W. T., Valle, O. V., et al. (2008) · Proteome Science · doi:10.1186/1477-5956-6-17 · Cited by 59 · see citing works
Synergy of the antibiotic colistin with echinocandin antifungals in Candida species
Zeidler, U., Bougnoux, M.-E., Lupan, A., Helynck, O., Doyen, A., Garcia, Z., Sertour, N., Clavaud, C., Munier-Lehmann, H., Saveanu, C., et al. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dks538 · Cited by 58 · see citing works
Regulation of expression, activity and localization of fungal chitin synthases
Rogg, L. E., Fortwendel, J. R., Juvvadi, P. R., & Steinbach, W. J. (2011) · Medical Mycology · doi:10.3109/13693786.2011.577104 · Cited by 59 · see citing works
Wolyniak, M. J., & Sundstrom, P. (2007) · Eukaryotic Cell · doi:10.1128/ec.00188-07 · Cited by 46 · see citing works
Off the wall: The rhyme and reason of Neurospora crassa hyphal morphogenesis
Verdín, J., Sánchez‐León, E., Rico-Ramírez, A. M., Martínez‐Núñez, L., Fajardo-Somera, R. A., & Riquelme, M. (2019) · The Cell Surface · doi:10.1016/j.tcsw.2019.100020 · Cited by 43 · see citing works
Cantero, P. D., & Ernst, J. F. (2011) · Molecular Microbiology · doi:10.1111/j.1365-2958.2011.07604.x · Cited by 40 · see citing works
Morcx, S., Kunz, C., Choquer, M., Assié, S., Blondet, E., Simond-Côte, E., Gajek, K., Chapeland‐Leclerc, F., Expert, D., & Soulié, M. (2012) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2012.11.011 · Cited by 38 · see citing works
Arbelet-Bonnin, D., Malfatti, P., Simond‐Côte, E., Fontaine, T., Desquilbet, L., Expert, D., Kunz, C., & Soulié, M. (2010) · Molecular Plant-Microbe Interactions · doi:10.1094/mpmi-02-10-0046 · Cited by 30 · see citing works
Kang, T. H., Hwang, E. I., Yun, B.-S., Park, K. D., Kwon, B. M., Shin, C. S., & Kim, S. U. (2007) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.30.598 · Cited by 29 · see citing works
Rico-Ramírez, A. M., Roberson, R. W., & Riquelme, M. (2018) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2018.03.006 · Cited by 26 · see citing works
Development of resources for the analysis of gene function in Pucciniomycotina red yeasts
Ianiri, G., Wright, S. A. I., Castoria, R., & Idnurm, A. (2011) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2011.03.003 · Cited by 26 · see citing works
Chitin Synthesis in Yeast: A Matter of Trafficking
Sánchez, N., & Roncero, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012251 · Cited by 23 · see citing works
Self-citationJia, C., Zhang, K., Zhang, D., Yu, Q., Zhao, Q., Xiao, C., Dong, Y., Chu, M., & Li, M. (2018) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2018.03.001 · Cited by 22 · see citing works
9 Chitin Synthesis and Fungal Cell Morphogenesis
Roncero, C., Sánchez‐Díaz, A., & Valdivieso, M. ‐. (2016) · Springer eBooks · doi:10.1007/978-3-319-27790-5_9 · Cited by 17 · see citing works
Self-citationThe Functional Specialization of Exomer as a Cargo Adaptor During the Evolution of Fungi
Antón-Plágaro, C., Taubas, J. V., & Roncero, C. (2018) · Genetics · doi:10.1534/genetics.118.300767 · Cited by 14 · see citing works
Self-citationSanz, M., Valle, R., & Roncero, C. (2007) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2007.00264.x · Cited by 11 · see citing works
Self-citationJiang, L., Xu, D., Hameed, A., Fang, T., Fazili, A. B. A., & Asghar, F. (2018) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2018.04.001 · Cited by 12 · see citing works
Degani, G., Ragni, E., Botias, P., Ravasio, D., Calderon, J., Pianezzola, E., Rodriguez-Peña, J. M., Vanoni, M. A., Arroyo, J., Fonzi, W. A., et al. (2016) · BMC Genomics · doi:10.1186/s12864-016-2853-5 · Cited by 10 · see citing works
Ramírez-Macías, I., Barlow, L. D., Antón-Plágaro, C., Spang, A., Roncero, C., & Dacks, J. B. (2018) · Scientific Reports · doi:10.1038/s41598-018-29416-4 · Cited by 9 · see citing works
Self-citationJiménez, C., Sacristán, C., Roncero, M. I. G., & Roncero, C. (2010) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2010.08.013 · Cited by 8 · see citing works
Self-citationGonzález-Téllez, S. V., & Riquelme, M. (2025) · Frontiers in Fungal Biology · doi:10.3389/ffunb.2024.1505388 · Cited by 6 · see citing works
One hundred years of the Spitzenkörper: A story in three acts
González-Téllez, S. V., Roberson, R. W., & Riquelme, M. (2025) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2025.104036 · Cited by 4 · see citing works
Manczinger, M., Bocsik, A., Kocsis, G. F., Vörös, A., Hegedüs, Z., Ördögh, L., Kondorosi, É., Marton, A., Vízler, C., Tubak, V., et al. (2015) · BioMed Research International · doi:10.1155/2015/398045 · Cited by 3 · see citing works
Song, C., Xue, A., Zhang, Z., Yang, L., Zhang, B., Zhang, M., Liu, Y., & Qin, J. (2026) · International Journal of Food Microbiology · doi:10.1016/j.ijfoodmicro.2026.111633 · Cited by 1 · see citing works
Easy-to-use imaging-cytometry assay to analyze chitin patterns in yeasts
Aldebert, D., Suarez, B., Bettega, F., Boucher, E., Garnaud, C., & Cornet, M. (2024) · Journal de Mycologie Médicale · doi:10.1016/j.mycmed.2024.101493 · Cited by 2 · see citing works
Rutas de glicosilación en Candida albicans: circuitos reguladores y efectos sobre virulencia
Cantero, M. D. P. D. (2010) · doi:10.14201/gredos.76428
Song, J., Wang, J., Hu, S., Gao, J., Liang, Z., Tan, S., & Zhao, H. (2026) · Mycopathologia · doi:10.1007/s11046-026-01071-8
- Authors
- Sanz, M., Carrano, L., Jiménez, C., Candiani, G., Trilla, J. A., Durán, A., & Roncero, C.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- Vicuron Pharmaceuticals, Gerenzano, Italy
- Instituto de Microbiología Bioquímica y Departamento de Microbiología y Genética, CSIC/Universidad de Salamanca, Edificio Departamental, R-219, Avda Campo Charro s/n, 37007 Salamanca, Spain
- Venue
- Microbiology
- Publisher
- Microbiology Society
- Published
- 2005-08-01
- Volume
- 151
- Issue
- 8
- Pages
- 2623-2636
- ISSN
- 1350-0872 (ISSN-L)
- 1465-2080
- OpenAlex
- W2021838894
- Cited by
- 32
- References
- 43
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2022: 2 · 2019: 1 · 2018: 5 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 0.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- Candida albicans, chitin synthesis, hyphal morphogenesis, fungal virulence, cell wall integrity, dimorphic transition, germ tube formation, septum formation, mouse infection model
- MeSH terms
- Animals, Candida albicans, Chitin Synthase, Membrane Proteins, Morphogenesis, Mutation, Virulence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review