THE AUR1 GENE IN SACCHAROMYCES-CEREVISIAE ENCODES DOMINANT RESISTANCE TO THE ANTIFUNGAL AGENT AUREOBASIDIN-A (LY295337)

THE AUR1 GENE IN SACCHAROMYCES-CEREVISIAE ENCODES DOMINANT RESISTANCE TO THE ANTIFUNGAL AGENT AUREOBASIDIN-A (LY295337)
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DOI:
10.1128/aac.39.12.2765
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发表时间:
1995-12-01
影响因子:
4.9
通讯作者:
RADDING, JA
RADDING, JA
中科院分区:
医学2区
文献类型:
--
作者:
HEIDLER, SA;RADDING, JA

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金黄色葡萄糖素A(LY295337)是一种具有抗念珠菌活性的环状深肽类抗真菌药物,其作用机制尚不清楚,LY295337对酿酒酵母LY295337也有抗菌活性,S突变株的选育报告了LY295337的抗药性。抗性存在于单个基因的显性突变中,该基因被命名为au1(金黄色葡萄糖素抗性),该基因被克隆和测序,在GenBank中搜索同源序列和BLAST没有阐明该基因的功能,尽管从酵母基因组测序项目和其他几个相邻的座位中发现了序列的同源性,但aur1的缺失是在二倍体的S酿酒酵母中完成的,随后对aur1/aur1 Delta二倍体的孢子形成和解剖导致了活孢子和非活孢子的2:2分离,表明aur1的缺失是致命的。由于LY295337具有杀菌作用,而aur1基因的缺失具有致死性,因此aur1基因可能成为LY295337的靶标。
Aureobasidin A (LY295337) is a cyclic depsipeptide antifungal agent with activity against Candida spp, The mechanism of action of LY295337 remains unknown, LY295337 also shows activity against the yeast Saccharomyces cerevisiae, Generation of a mutant of S, cerevisiae resistant to LY295337 is reported. Resistance was found to reside in a dominant mutation of a single gene,which has been named AUR1 (for aureobasidin resistance), This gene was cloned and sequenced, A search for homologous sequences in GenBank and by BLAST did not elucidate the function of this gene, although sequence homology to an open reading frame from the Saccharomyces genome sequencing project and several other adjacent loci was noted, Deletion of aur1 was accomplished in a diploid S, cerevisiae strain, Subsequent sporulation and dissection of the aur1/aur1 Delta diploid resulted in tetrads demonstrating 2:2 segregation of viable and nonviable spores, indicating that deletion of aur1 Is lethal. As LY295337 is fungicidal and deletion of aur1 is lethal, aur1 represents a potential candidate for the target of LY295337.