Genetic and phenotypic intra-species variation in Candida albicans.

Genome Res
Authors
Keywords
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.

Year of Publication
2015
Journal
Genome Res
Volume
25
Issue
3
Pages
413-25
Date Published
2015 Mar
ISSN
1549-5469
URL
DOI
10.1101/gr.174623.114
PubMed ID
25504520
PubMed Central ID
PMC4352881
Links
Grant list
HHSN272200900018C / AI / NIAID NIH HHS / United States
AI081704 / AI / NIAID NIH HHS / United States
R21 AI112363 / AI / NIAID NIH HHS / United States
AI0624273 / AI / NIAID NIH HHS / United States
R01 AI075096 / AI / NIAID NIH HHS / United States
HHSN272200900018C / PHS HHS / United States
AI075096-S1 / AI / NIAID NIH HHS / United States
F31DE023726 / DE / NIDCR NIH HHS / United States
F31 DE023726 / DE / NIDCR NIH HHS / United States
AI075096 / AI / NIAID NIH HHS / United States
AI112363 / AI / NIAID NIH HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States
R01 AI081704 / AI / NIAID NIH HHS / United States