Zwiers Lute-Harm, Stergiopoulos Ioannis, Van Nistelrooy Johannes G M, De Waard Maarten A
Laboratory of Phytopathology, Wageningen University, The Netherlands.
Antimicrob Agents Chemother. 2002 Dec;46(12):3900-6. doi: 10.1128/AAC.46.12.3900-3906.2002.
Laboratory strains of Mycosphaerella graminicola with decreased susceptibilities to the azole antifungal agent cyproconazole showed a multidrug resistance phenotype by exhibiting cross-resistance to an unrelated chemical, cycloheximide or rhodamine 6G, or both. Decreased azole susceptibility was found to be associated with either decreased or increased levels of accumulation of cyproconazole. No specific relationship could be observed between azole susceptibility and the expression of ATP-binding cassette (ABC) transporter genes MgAtr1 to MgAtr5 and the sterol P450 14alpha-demethylase gene, CYP51. ABC transporter MgAtr1 was identified as a determinant in azole susceptibility since heterologous expression of the protein reduced the azole susceptibility of Saccharomyces cerevisiae and disruption of MgAtr1 in one specific M. graminicola laboratory strain with constitutive MgAtr1 overexpression restored the level of susceptibility to cyproconazole to wild-type levels. However, the level of accumulation in the mutant with an MgAtr1 disruption did not revert to the wild-type level. We propose that variations in azole susceptibility in laboratory strains of M. graminicola are mediated by multiple mechanisms.
对唑类抗真菌剂环丙唑醇敏感性降低的禾谷格孢腔菌实验室菌株，通过对一种不相关化学物质环己酰亚胺或罗丹明6G或两者表现出交叉抗性，呈现出多药耐药表型。发现唑类敏感性降低与环丙唑醇积累水平的降低或增加有关。在唑类敏感性与ATP结合盒（ABC）转运蛋白基因MgAtr1至MgAtr5以及甾醇P450 14α-脱甲基酶基因CYP51的表达之间未观察到特定关系。ABC转运蛋白MgAtr1被确定为唑类敏感性的一个决定因素，因为该蛋白的异源表达降低了酿酒酵母的唑类敏感性，并且在一个具有组成型MgAtr1过表达的特定禾谷格孢腔菌实验室菌株中破坏MgAtr1，可将对环丙唑醇的敏感性水平恢复到野生型水平。然而，MgAtr1破坏突变体中的积累水平并未恢复到野生型水平。我们认为，禾谷格孢腔菌实验室菌株中唑类敏感性的变化是由多种机制介导的。
