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Genome Res. 2015 Mar;25(3):413-25. doi: 10.1101/gr.174623.114. Epub 2014 Dec 11.

Genetic and phenotypic intra-species variation in Candida albicans.

Author information

1
Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA;
2
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA;
3
Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA; Department of Molecular, Cellular Biology and Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA;
4
Department of Molecular, Cellular Biology and Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA; Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv 69978, Israel.
5
Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA; richard_bennett@brown.edu cuomo@broadinstitute.org.
6
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA; richard_bennett@brown.edu cuomo@broadinstitute.org.

Abstract

Candida albicans is a commensal fungus of the human gastrointestinal tract and a prevalent opportunistic pathogen. To examine diversity within this species, extensive genomic and phenotypic analyses were performed on 21 clinical C. albicans isolates. Genomic variation was evident in the form of polymorphisms, copy number variations, chromosomal inversions, subtelomeric hypervariation, loss of heterozygosity (LOH), and whole or partial chromosome aneuploidies. All 21 strains were diploid, although karyotypic changes were present in eight of the 21 isolates, with multiple strains being trisomic for Chromosome 4 or Chromosome 7. Aneuploid strains exhibited a general fitness defect relative to euploid strains when grown under replete conditions. All strains were also heterozygous, yet multiple, distinct LOH tracts were present in each isolate. Higher overall levels of genome heterozygosity correlated with faster growth rates, consistent with increased overall fitness. Genes with the highest rates of amino acid substitutions included many cell wall proteins, implicating fast evolving changes in cell adhesion and host interactions. One clinical isolate, P94015, presented several striking properties including a novel cellular phenotype, an inability to filament, drug resistance, and decreased virulence. Several of these properties were shown to be due to a homozygous nonsense mutation in the EFG1 gene. Furthermore, loss of EFG1 function resulted in increased fitness of P94015 in a commensal model of infection. Our analysis therefore reveals intra-species genetic and phenotypic differences in C. albicans and delineates a natural mutation that alters the balance between commensalism and pathogenicity.

PMID:
25504520
PMCID:
PMC4352881
DOI:
10.1101/gr.174623.114
[Indexed for MEDLINE]
Free PMC Article

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