Homozygosity at the MTL locus in clinical strains of Candida albicans: karyotypic rearrangements and tetraploid formation†
Abstract
One hundred and twenty Candida albicans clinical isolates from the late 1980s and early 1990s were examined for homozygosity at the MTL locus. Of these, 108 were heterozygous (MTLa/MTLalpha), whereas seven were MTLa and five were MTLalpha. Five of the homozygous isolates were able to switch to the opaque cell morphology, while opaque cells were not detectable among the remaining seven. Nevertheless, all but one of the isolates homozygous at the MTL locus were shown to mate and to yield cells containing markers from both parents; the non-mater was found to have a frameshift in the MTLalpha1 gene. In contrast to Saccharomyces cerevisiae, C. albicans homozygotes with no active MTL allele failed to mate rather than mating as a cells. There was no correlation between homozygosity and fluconazole resistance, mating and fluconazole resistance or switching and fluconazole resistance, in part because most of the strains were isolated before the widespread use of this antifungal agent, and only three were in fact drug resistant. Ten of the 12 homozygotes had rearranged karyotypes involving one or more homologue of chromosomes 4, 5, 6 and 7. We suggest that karyotypic rearrangement, drug resistance and homozygosity come about as the result of induction of hyper-recombination during the infection process; hence, they tend to occur together, but each is the independent result of the same event. Furthermore, as clinical strains can mate and form tetraploids, mating and marker exchange are likely to be a significant part of the life cycle of C. albicans in vivo.
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Tetraploid C. albicans cells can generate diverse fitness and heterogeneity through increased rates of heterozygosity loss.
“The discovery of tetraploid cells of C. albicans, containing four homologous sets of chromosomes, and their ability to generate a diverse range of fitness and heterogeneity through increased rates of heterozygosity loss”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus<i>Candida albicans</i> (2020) · cites this paper as [157]
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- Authors
- Legrand, M., Lephart, P., Forche, A., Mueller, F. C., Walsh, T., Magee, P. T., & Magee, B. B.
- Affiliations
- University of Minnesota (US)
- National Institutes of Health (US)
- Heidelberg University (DE)
- Corresponding author
- Magee, P.T.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2004-04-28
- Volume
- 52
- Issue
- 5
- Pages
- 1451-1462
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1942332747
- Cited by
- 110
- References
- 32
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 7 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 14 · 2013: 7 · 2012: 1
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Minnesota
- National Institutes of Health (n01ai005406-000)
- National Cancer Institute (P30CA-77598, P30CA077598)
- National Institute of General Medical Sciences (T32GM008347, T32-GM-08347)
- National Institute of Allergy and Infectious Diseases (AI-16567, AI05406, AI46351, R01AI016567, R01AI046351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
- Keywords
- Candida albicans, mating-type locus, homozygosity, tetraploidy, mating, fluconazole resistance, hyper-recombination, clinical isolates
- MeSH terms
- Alleles, Antifungal Agents, Candida albicans, Candidiasis, Drug Resistance, Microbial, Homozygote, Humans, Karyotyping, Ploidies, Polymorphism, Genetic, Recombination, Genetic, Saccharomyces cerevisiae, Fluconazole, Gene Expression Regulation, Fungal
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