The evolution of drug resistance in clinical isolates of Candida albicans
Name
Ford-2014-The evolution of dru.pdf
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3.19 MB
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Adobe PDF
Checksum (MD5)
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Author(s)
Abbey, Darren A.
Issi, Luca
Guiducci, Candace
Martinez, Diego A
Delorey, Toni
Li, Bi yu
White, Theodore C
Cuomo, Christina
Rao, Reeta P
Berman, Judith
Date Issued
February 2015
Journal
eLife
Publisher
eLife Sciences Publications, Ltd.
Citation
Ford, Christopher B, Jason M Funt, Darren Abbey, Luca Issi, Candace Guiducci, Diego A Martinez, Toni Delorey, et al. “ The Evolution of Drug Resistance in Clinical Isolates of Candida Albicans .” eLife 4 (February 3, 2015).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.7554/eLife.00662
