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The evolution of drug resistance in clinical isolates of Candida albicans
Journal article

The evolution of drug resistance in clinical isolates of Candida albicans

  • Ford, Christopher B Broad Institute of MIT and Harvard, Cambridge, United States
  • Funt, Jason M Broad Institute of MIT and Harvard, Cambridge, United States
  • Abbey, Darren Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, United States
  • Issi, Luca Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, United States
  • Guiducci, Candace Broad Institute of MIT and Harvard, Cambridge, United States
  • Martinez, Diego A Broad Institute of MIT and Harvard, Cambridge, United States
  • Delorey, Toni ORCID Broad Institute of MIT and Harvard, Cambridge, United States
  • Li, Bi yu Broad Institute of MIT and Harvard, Cambridge, United States
  • White, Theodore C School of Biological Sciences, University of Missouri at Kansas City, Kansas City, United States
  • Cuomo, Christina ORCID Broad Institute of MIT and Harvard, Cambridge, United States
  • Rao, Reeta P Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, United States
  • Berman, Judith Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Tel Aviv, Israel
  • Thompson, Dawn A Broad Institute of MIT and Harvard, Cambridge, United States
  • Regev, Aviv Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, United States
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  • 2015-2-3
Published in:
  • eLife. - eLife Sciences Publications, Ltd. - 2015, vol. 4
English 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.
Language
  • English
Open access status
gold
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Persistent URL
https://sonar.ch/global/documents/273999
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