Functional specificity of Candida albicans Als3p proteins and clade specificity of ALS3 alleles discriminated by the number of copies of the tandem repeat sequence in the central domain
Abstract
Candida albicans strain SC5314 contains two ALS3 alleles, which differ in sequence with respect to the number of copies of the 108 bp tandem repeat sequence within the central domain of the coding region. One allele (ALS3(12)) has 12 tandem repeat copies while the other (ALS3(9)) has 9 copies. Wild-type C. albicans(ALS3(12)/ALS3(9)) and those containing various ALS3 alleles (ALS3(12)/als3 Δ(9),als3 Δ(12)/ALS3(9) and als3 Δ(12)/als3 Δ(9)) were assayed for adhesion to monolayers of cultured vascular endothelial and pharyngeal epithelial cells. These assays showed obvious adhesive function for the larger Als3p protein, compared to a minor contribution to adhesion from the smaller protein. These functional differences in strain SC5314 prompted examination of ALS3 allelic diversity across the five major genetic clades of C. albicans. This analysis focused on the number of copies of the tandem repeat sequence within the central domain of the coding region and showed a range of alleles encoding from 6 to 19 tandem repeat copies. Clades differed with respect to prevalent ALS3 alleles and allele distribution, but were similar for the mean number of tandem repeat copies per ALS3 allele. Analysis of allelic pairing showed clade differences and the tendency for C. albicans strains to encode one longer and one shorter ALS3 allele. The allelic variability observed for ALS3 and its functional consequences observed in strain SC5314 highlight the importance of understanding ALS allelic diversity in order to draw accurate conclusions about Als protein function.
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An als3Δ/als3Δ null mutant had reduced adherence to endothelial cells, buccal epithelial cells, and FaDu epithelial cells.
“It has been reported by others that an als3D/als3D null mutant had reduced adherence to endothelial cells, buccal epithelial cells, and FaDu epithelial cells [24,35].”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [35]
Versions of Als3 with fewer tandem repeats mediated less adherence than did versions of Als3 with more tandem repeats.
“Similarly, Oh et al. [35] found that versions of Als3 with fewer tandem repeats mediated less adherence than did versions of Als3 with more tandem repeats.”
From Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells (2007) · cites this paper as [35]
Cites
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Self-citationFu, Y., Ibrahim, A. S., Sheppard, D. C., Chen, Y., French, S. W., Cutler, J. E., Filler, S. G., & Edwards, J. E. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02873.x · Cited by 218 · see citing works
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“The ALS (agglutinin-like sequence) gene family of Candida albicans encodes eight large cell-surface glycoproteins, some of which function in adhesion to host cells ( Gaur & Klotz, 1997; Hoyer, 2001; Fu et al., 2002; Zhao et al., 2004).”
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Als3 Is a Candida albicans Invasin That Binds to Cadherins and Induces Endocytosis by Host Cells
Phan, Q. T., Myers, C. L., Fu, Y., Sheppard, D. C., Yeaman, M. R., Welch, W. H., Ibrahim, A. S., Edwards, J. E., & Filler, S. G. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050064 · Cited by 641 · see citing works
<i>Candida albicans</i> Cell Wall Proteins
Chaffin, W. L. (2008) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00032-07 · Cited by 515 · see citing works
Hoyer, L. L., Green, C. B., Oh, S.-H., & Zhao, X. (2008) · Medical Mycology · doi:10.1080/13693780701435317 · Cited by 356 · see citing works
Self-citationCandida albicans Als3, a multifunctional adhesin and invasin
Liu, Y., & Filler, S. G. (2011) · Eukaryotic Cell · doi:10.1128/ec.00279-10 · Cited by 354 · see citing works
Adhesins in human fungal pathogens: glue with plenty of stick.
de Groot, P. W. J., Bader, O., de Boer, A. D., Weig, M., & Chauhan, N. (2013) · Eukaryotic Cell · doi:10.1128/ec.00364-12 · Cited by 319 · see citing works
Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen
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Calderon, J., Zavrel, M., Ragni, E., Fonzi, W. A., Rupp, S., & Popolo, L. (2010) · Microbiology · doi:10.1099/mic.0.038000-0 · Cited by 72 · see citing works
Structure and Function of Glycosylated Tandem Repeats from Candida albicans Als Adhesins
Frank, A. T., Ramsook, C. B., Otoo, H. N., Tan, C., Soybelman, G., Rauceo, J. M., Gaur, N. K., Klotz, S. A., & Lipke, P. N. (2010) · Eukaryotic Cell · doi:10.1128/ec.00235-09 · Cited by 63 · see citing works
Dunkel, N., & Morschhäuser, J. (2011) · Eukaryotic Cell · doi:10.1128/ec.00281-10 · Cited by 20 · see citing works
- Authors
- Oh, S.-H., Cheng, G., Nuessen, J. A., Jajko, R., Yeater, K. M., Zhao, X., Pujol, C., Soll, D. R., & Hoyer, L. L.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- University of Iowa (US)
- Venue
- Microbiology
- Publisher
- Microbiology Society
- Published
- 2005-03-01
- Volume
- 151
- Issue
- 3
- Pages
- 673-681
- ISSN
- 1350-0872 (ISSN-L)
- 1465-2080
- OpenAlex
- W2125994797
- Cited by
- 108
- References
- 4
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 13 · 2013: 7 · 2012: 2
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI-2392)
- National Institute of Dental and Craniofacial Research (R01DE014158, DE 14158)
- 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, tandem repeats, allelic diversity, cell adhesion, SC5314, fungal adhesins
- MeSH terms
- Alleles, Candida albicans, Cell Adhesion, Cells, Cultured, Endothelium, Vascular, Fungal Proteins, Humans, Pharynx, Umbilical Veins, Gene Expression Regulation, Fungal, Gene Dosage, Tandem Repeat Sequences, Endothelial Cells
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