Identification and Characterization of Four Azole-Resistant erg3 Mutants of Candida albicans
Identification and Characterization of Four Azole-Resistant erg3 Mutants of Candida albicans
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DOI：
10.1128/aac.00348-10
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发表时间：
2010-11-01
影响因子：
4.9
通讯作者：
Kelly, Steven L.
中科院分区：
文献类型：
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作者：
Martel, Claire M.;Parker, Josie E.;Kelly, Steven L.
甾醇分析鉴定了四种白色念珠菌erg 3突变体，其中麦角甾7，22-二烯醇（指示甾醇δ（5，6）-去饱和酶（Erg 3 p）活性的扰动）占总甾醇级分的>5%。在标准CLSI检测条件下，erg 3突变体（CA 12、CA 488、CA 490和CA 1008）均对氟康唑、伏立康唑、伊曲康唑、酮康唑和克霉唑耐药（MIC值分别>= 256、16、16、8和1 μ g/ml）。重要的是，CA 12和CA 1008保留了唑类耐药表型，即使在FK 506（一种多药外排抑制剂）存在下进行检测。相反，CA 488、CA 490和三个比较分离株（CA 6、CA 14和CA 177，其中麦角固醇占总固醇级分的>80%，并且麦角甾7，22-二烯醇不可检测）在流出抑制测定条件下均显示唑敏感表型。由于它们的麦角甾醇含量，CA 6、CA 14和CA 177对阿替霉素B高度敏感（MIC值，< 0.25 μ g ml（-1））; CA 1008，其中麦角甾醇包含
Sterol analysis identified four Candida albicans erg3 mutants in which ergosta 7,22-dienol, indicative of perturbations in sterol Delta(5,6)-desaturase (Erg3p) activity, comprised >5% of the total sterol fraction. The erg3 mutants (CA12, CA488, CA490, and CA1008) were all resistant to fluconazole, voriconazole, itraconazole, ketoconazole, and clotrimazole under standard CLSI assay conditions (MIC values, >= 256, 16, 16, 8, and 1 mu g ml(-1), respectively). Importantly, CA12 and CA1008 retained an azole-resistant phenotype even when assayed in the presence of FK506, a multidrug efflux inhibitor. Conversely, CA488, CA490, and three comparator isolates (CA6, CA14, and CA177, in which ergosterol comprised >80% of the total sterol fraction and ergosta 7,22-dienol was undetectable) all displayed azole-sensitive phenotypes under efflux-inhibited assay conditions. Owing to their ergosterol content, CA6, CA14, and CA177 were highly sensitive to amphotericin B (MIC values, < 0.25 mu g ml(-1)); CA1008, in which ergosterol comprised