Molecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates from Shanghai, China

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• 作者：Cuiyun Zhu^a ; Yongxin Zhang^b ; Yinzhong Shen^a ; Gilman Kit Hang Siu^c ; Wenjuan Wu^a ; Xueqin Qian^a ; Guilin Deng^a ; Yan Xu^a ; Ricky Lau^c ; Xiaoyong Fan^a ; Wenhong Zhang^b ; Hongzhou Lu^a ; ^b ; ¹ ; Wing-Cheong Yam^c ; ¹ ; ^{wcyam@hkucc.hku.hk}
• 关键词：Mycobacterium tuberculosis ; Fluoroquinolone resistance ; Gyrase mutations
• 刊名：Diagnostic Microbiology and Infectious Disease
• 出版年：2012
• 期刊代码：79_07328893
• 类别：med
• 出版时间：July, 2012
• 卷：73
• 期：3
• 页码：260-263
• 文件大小：167 K

摘要

China is one of the countries with the highest prevalence of fluoroquinolone-resistant (FQ^r) Mycobacterium tuberculosis. Nevertheless, knowledge on the molecular characterization of the FQ^r M. tuberculosis strains of this region remains very limited. This study was performed to investigate the frequencies and types of mutations present in FQ^r M. tuberculosis clinical isolates collected in Shanghai, China. A total of 206 FQ^r M. tuberculosis strains and 21 ofloxacin-sensitive (FQ^s) M. tuberculosis strains were isolated from patients with pulmonary tuberculosis in Shanghai. The phenotypic drug susceptibilities were determined by the proportion method, and the mutations inside quinolone resistance-determining region (QRDR) of gyrA and gyrB genes were identified by DNA sequence analyses. Among 206 FQ^r M. tuberculosis strains, 44%(90/206) were multidrug-resistant isolates and 39%(81/206) were extensively drug-resistant isolates. Only 9%(19/206) were monoresistant to ofloxacin. In total, 79.1%(163/206) of FQ^r isolates harboured mutations in either gyrA or gyrB QRDR. Mutations in gyrA QRDR were found in 75.7%(156/206) of FQ^r clinical isolates. Among those gyrA mutants, a majority (75.6%) harboured mutations at amino acid position 94, with D94G being the most frequent amino acid substitution. Mutations in gyrA QRDR showed 100%positive predictive value for FQ^r M. tuberculosis in China. Mutations in gyrB were observed in 15.5%(32/206) of FQ^r clinical isolates. Ten novel mutations were identified in gyrB. However, most of them also harboured mutations in gyrA, limiting their contribution to FQ^r resistance in M. tuberculosis. Our findings indicated that, similar to other geographic regions, mutations in gyrA were shown to be the major mechanism of FQ^r resistance in M. tuberculosis isolates. The mutations in gyrA QRDR can be a good molecular surrogate marker for detecting FQ^r M. tuberculosis in China.