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[智利白色念珠菌临床分离株中唑类耐药机制的特征分析]

[Characterization of azole resistance mechanisms in Chilean clinical isolates of Candida albicans].

作者信息

Fuentes Marisol, Hermosilla Germán, Alburquenque Claudio, Falconer Mary A, Amaro José, Tapia Cecilia

出版信息

Rev Chilena Infectol. 2014 Oct;31(5):511-7. doi: 10.4067/S0716-10182014000500001.

Abstract

INTRODUCTION

The commensal yeast Candida albicans, can cause superficial or systemic candidiasis in susceptible hosts. In Chile, azole antifungals are the most widely used drugs in the treatment of candidiasis. In a previous study performed at our center, 2.1 and 1.6% of clinical isolates of C. albicans were found to be resistant to fluconazole and voriconazole, respectively.

OBJECTIVE

To characterize the resistance mechanisms involved in azoles resistance in Chilean clinical isolates.

METHODOLOGY

Eight resistant, nine susceptible-dose dependent (SDD) and 10 susceptible strains (n: 27) were selected according to the Clinical Laboratory Standards Institute (CLSI) M27-S3 criteria, from vaginal and urine samples. Mutations in the 408-488 region of the ERG11 gene were studied by sequencing, and the relative expression of ERG11 gene and efflux pump genes CDR1, CDR2 and MDR1, was evaluated by quantitative real-time PCR (q-PCR).

RESULTS

No mutations were detected in the ERG11 gene and its overexpression was found only in 12.5% of the resistant strains (1/8). The most prevalent mechanism of resistance was the over-expression of efflux pumps (62.5%; 5/8).

CONCLUSION

The study of the expression of efflux pumps by q-PCR could be a useful diagnostic tool for early detection of azole resistance in C. albicans.

摘要

引言

共生酵母菌白色念珠菌可在易感宿主中引起浅表或全身性念珠菌病。在智利,唑类抗真菌药物是治疗念珠菌病最广泛使用的药物。在我们中心之前进行的一项研究中,发现白色念珠菌临床分离株中分别有2.1%和1.6%对氟康唑和伏立康唑耐药。

目的

表征智利临床分离株中唑类耐药所涉及的耐药机制。

方法

根据临床实验室标准协会(CLSI)M27-S3标准,从阴道和尿液样本中选取8株耐药菌株、9株剂量依赖敏感(SDD)菌株和10株敏感菌株(n = 27)。通过测序研究ERG11基因408-488区域的突变,并通过定量实时PCR(q-PCR)评估ERG11基因以及外排泵基因CDR1、CDR2和MDR1的相对表达。

结果

未在ERG11基因中检测到突变,仅在12.5%的耐药菌株(1/8)中发现其过表达。最普遍的耐药机制是外排泵的过表达(62.5%;5/8)。

结论

通过q-PCR研究外排泵的表达可能是早期检测白色念珠菌唑类耐药的有用诊断工具。

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