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Elife DOI:10.7554/eLife.00662

The evolution of drug resistance in clinical isolates of Candida albicans.

Publication TypeJournal Article
Year of Publication2015
AuthorsFord, CB, Funt, JM, Abbey, D, Issi, L, Guiducci, C, Martinez, DA, Delorey, T, Li, BYu, White, TC, Cuomo, C, Rao, RP, Berman, J, Thompson, DA, Regev, A
JournalElife
Volume4
Pagese00662
Date Published2015 Feb 03
ISSN2050-084X
KeywordsAdhesiveness, Aneuploidy, Candida albicans, Candidiasis, Drug Resistance, Fungal, Evolution, Molecular, Fluconazole, Genetic Fitness, Genome, Human, Host-Pathogen Interactions, Humans, Loss of Heterozygosity, Microbial Sensitivity Tests, Mutation, Phenotype, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Virulence
Abstract

Candida albicans is both a member of the healthy human microbiome and a major pathogen in immunocompromised individuals. Infections are typically treated with azole inhibitors of ergosterol biosynthesis often leading to drug resistance. Studies in clinical isolates have implicated multiple mechanisms in resistance, but have focused on large-scale aberrations or candidate genes, and do not comprehensively chart the genetic basis of adaptation. Here, we leveraged next-generation sequencing to analyze 43 isolates from 11 oral candidiasis patients. We detected newly selected mutations, including single-nucleotide polymorphisms (SNPs), copy-number variations and loss-of-heterozygosity (LOH) events. LOH events were commonly associated with acquired resistance, and SNPs in 240 genes may be related to host adaptation. Conversely, most aneuploidies were transient and did not correlate with drug resistance. Our analysis also shows that isolates also varied in adherence, filamentation, and virulence. Our work reveals new molecular mechanisms underlying the evolution of drug resistance and host adaptation.

URLhttp://dx.doi.org/10.7554/eLife.00662
DOI10.7554/eLife.00662
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25646566?dopt=Abstract

Alternate JournalElife
PubMed ID25646566
PubMed Central IDPMC4383195
Grant ListR01 CA119176 / CA / NCI NIH HHS / United States
DP1 CA174427 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
2R01CA119176-01 / CA / NCI NIH HHS / United States
8DP1CA174427 / CA / NCI NIH HHS / United States