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      Chromosome 5 monosomy of Candida albicans controls susceptibility to various toxic agents, including major antifungals.

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          Abstract

          Candida albicans is a prevailing fungal pathogen with a diploid genome that can adapt to environmental stresses by losing or gaining an entire chromosome or a large portion of a chromosome. We have previously found that the loss of one copy of chromosome 5 (Ch5) allows for adaptation to the toxic sugar l-sorbose. l-Sorbose is similar to caspofungin and other antifungals from the echinocandins class, in that it represses synthesis of cell wall glucan in fungi. Here, we extended the study of the phenotypes controlled by Ch5 copy number. We examined 57 strains, either disomic or monosomic for Ch5 and representing five different genetic backgrounds, and found that the monosomy of Ch5 causes elevated levels of chitin and repressed levels of 1,3-β-glucan components of the cell wall, as well as diminished cellular ergosterol. Increased deposition of chitin in the cell wall could be explained, at least partially, by a 2-fold downregulation of CHT2 on the monosomic Ch5 that encodes chitinase and a 1.5-fold upregulation of CHS7 on Ch1 that encodes the protein required for wild-type chitin synthase III activity. Other important outcomes of Ch5 monosomy consist of susceptibility changes to agents representing four major classes of antifungals. Susceptibility to caspofungin increased or decreased and susceptibility to 5-fluorocytosine decreased, whereas susceptibility to fluconazole and amphotericin B increased. Our results suggest that Ch5 monosomy represents an unrecognized C. albicans regulatory strategy that impinges on multiple stress response pathways.

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          Author and article information

          Journal
          Antimicrob. Agents Chemother.
          Antimicrobial agents and chemotherapy
          American Society for Microbiology
          1098-6596
          0066-4804
          Oct 2013
          : 57
          : 10
          Affiliations
          [1 ] Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, USA.
          Article
          AAC.00516-13
          10.1128/AAC.00516-13
          3811469
          23896475
          3fe925d3-774f-41f5-adc9-e52e004bf0c2
          History

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