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首页> 外文期刊>The Journal of Antimicrobial Chemotherapy >Mechanisms of azole resistance in 52 clinical isolates of Candida tropicalis in China
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Mechanisms of azole resistance in 52 clinical isolates of Candida tropicalis in China

机译：中国52株热带念珠菌临床分离株的唑耐药机制。

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Objectives: To explore the mechanisms underlying azole resistance in clinical isolates of Candida tropicalis collected in China by focusing on their efflux pumps, respiratory status and azole antifungal target enzyme. Methods: Fifty-two clinical isolates of C. tropicalis were collected from five hospitals in four provinces of China and antifungal susceptibility tests were performed. Rhodamine 6G and rhodamine 123 were used to investigate the efflux pumps and respiratory status, respectively. Transporter-related genes CDR1 and MDR1, mitochondrial gene CYTb, as well as ERG11, were quantified by real-time RT-PCR. Meanwhile, ergosterol content was analysed using liquid chromatography-mass spectrometry/mass spectrometry. An ERG11-deficient (erg11D) Saccharomyces cerevisiae strain was generated to study the function of mutations in ERG11. Results: MICs showed that 31 isolates were resistant to at least one type of azole antifungal. Flow cytometry using rhodamine 123 revealed increased respiration for the azole-resistant isolates, but CYTb was not overexpressed. No significant difference in the efflux of rhodamine 6G was found, which was consistent with the comparable expression levels of CDR1 and MDR1. In contrast, the azole-resistant isolates overexpressed ERG11 and showed increased ergosterol content. Moreover, the isolates resistant to three azole antifungals expressed higher levels of ERG11 mRNA than those resistant to only fluconazole or itraconazole. Two ERG11 mutations, Y132F and S154F, were found in azole-resistant isolates and could be shown to mediate azole resistance by expression in S. cerevisiae. ? The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
机译：目的：通过对中国热带假丝酵母的外排泵，呼吸状态和唑类抗真菌靶酶的研究，探讨其对唑类耐药的潜在机制。方法：从中国四个省的五家医院中收集了52株热带假丝酵母临床分离株，并进行了抗真菌药敏试验。罗丹明6G和罗丹明123分别用于调查外排泵和呼吸状态。转运相关基因CDR1和MDR1，线粒体基因CYTb以及ERG11通过实时RT-PCR进行定量。同时，使用液相色谱-质谱/质谱分析麦角固醇含量。产生一个ERG11缺陷型（erg11D）酿酒酵母菌株以研究ERG11中突变的功能。结果：MICs显示31株分离株对至少一种唑类抗真菌药具有抗性。使用若丹明123的流式细胞仪显示，抗唑类细菌的呼吸增加，但CYTb并未过表达。罗丹明6G外排没有发现显着差异，这与CDR1和MDR1的可比表达水平一致。相比之下，耐唑类分离株过表达ERG11，并显示麦角固醇含量增加。此外，与仅对氟康唑或伊曲康唑有抗药性的菌株相比，对三种唑类抗真菌药具有抗性的菌株表达的ERG11 mRNA水平更高。在耐唑的菌株中发现了两个ERG11突变Y132F和S154F，它们可以通过在酿酒酵母中表达来介导对唑的抗性。 ？作者2012。由牛津大学出版社代表英国抗菌化学协会出版。

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