title: Chromosome 5 of Human Pathogen Candida albicans Carries Multiple Genes for Negative Control of Caspofungin and Anidulafungin Susceptibility.
abstract: Candida albicans is an important fungal pathogen with a diploid genome that can adapt to caspofungin, a major drug from the echinocandin class, by a reversible loss of one copy of chromosome 5 (Ch5). Here, we explore a hypothesis that more than one gene for negative regulation of echinocandin tolerance is carried on Ch5. We constructed C. albicans strains that each lacked one of the following Ch5 genes: CHT2 for chitinase, PGA4 for glucanosyltransferase, and CSU51, a putative transcription factor. We demonstrate that independent deletion of each of these genes increased tolerance for caspofungin and anidulafungin, another echinocandin. Our data indicate that Ch5 carries multiple genes for negative control of echinocandin tolerance, although the final number has yet to be established.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Sumanun
authors.initials: S
authors.lastname: Suwunnakorn
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Hironao
authors.initials: H
authors.lastname: Wakabayashi
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, USA elena_bulgac@urmc.rochester.edu.
authors.forename: Elena
authors.initials: E
authors.lastname: Rustchenko
mesh_terms: D000077612:Anidulafungin; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D000077336:Caspofungin; D002688:Chitinases / Q000172:deficiency / Q000235:genetics; D002874:Chromosome Mapping; D015825:Chromosomes, Fungal / Q000737:chemistry*; D025141:Drug Resistance, Fungal / Q000235:genetics*; D004361:Drug Tolerance / Q000235:genetics*; D054714:Echinocandins / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D016695:Glycosyltransferases / Q000172:deficiency / Q000235:genetics; D006801:Humans; D055666:Lipopeptides / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D014157:Transcription Factors; D000077612:Anidulafungin; D016695:Glycosyltransferases; D002688:Chitinases; D000077336:Caspofungin