Suwunnakorn Sumanun, Wakabayashi Hironao, Rustchenko Elena
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, USA.
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York, USA
Antimicrob Agents Chemother. 2016 Nov 21;60(12):7457-7467. doi: 10.1128/AAC.01888-16. Print 2016 Dec.
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.
白色念珠菌是一种重要的真菌病原体，具有二倍体基因组，它可通过可逆性丢失5号染色体（Ch5）的一个拷贝来适应棘白菌素类的主要药物卡泊芬净。在此，我们探讨一个假说，即Ch5上携带不止一个对棘白菌素耐受性起负调控作用的基因。我们构建了白色念珠菌菌株，每个菌株分别缺失以下Ch5基因之一：几丁质酶基因CHT2、葡聚糖基转移酶基因PGA4以及一个假定的转录因子CSU51。我们证明，独立缺失这些基因中的每一个都会增加对卡泊芬净和另一种棘白菌素阿尼芬净的耐受性。我们的数据表明，Ch5携带多个对棘白菌素耐受性起负调控作用的基因，尽管最终数量尚未确定。
