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

Cuiyun Zhu, Yongxin Zhang, Yinzhong Shen, Kit Hang Siu, Wenjuan Wu, Xueqin Qian, Guilin Deng, Yan Xu, Ricky Lau, Xiaoyong Fan, Wenhong Zhang, Hongzhou Lu, Wing Cheong Yam

Research output: Journal article publicationJournal articleAcademic researchpeer-review

18 Citations (Scopus)

Abstract

China is one of the countries with the highest prevalence of fluoroquinolone-resistant (FQr) Mycobacterium tuberculosis. Nevertheless, knowledge on the molecular characterization of the FQrM. tuberculosis strains of this region remains very limited. This study was performed to investigate the frequencies and types of mutations present in FQrM. tuberculosis clinical isolates collected in Shanghai, China. A total of 206 FQrM. tuberculosis strains and 21 ofloxacin-sensitive (FQs) 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 FQrM. 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 FQrisolates harboured mutations in either gyrA or gyrB QRDR. Mutations in gyrA QRDR were found in 75.7% (156/206) of FQrclinical 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 FQrM. tuberculosis in China. Mutations in gyrB were observed in 15.5% (32/206) of FQrclinical isolates. Ten novel mutations were identified in gyrB. However, most of them also harboured mutations in gyrA, limiting their contribution to FQrresistance in M. tuberculosis. Our findings indicated that, similar to other geographic regions, mutations in gyrA were shown to be the major mechanism of FQrresistance in M. tuberculosis isolates. The mutations in gyrA QRDR can be a good molecular surrogate marker for detecting FQrM. tuberculosis in China.
Original languageEnglish
Pages (from-to)260-263
Number of pages4
JournalDiagnostic Microbiology and Infectious Disease
Volume73
Issue number3
DOIs
Publication statusPublished - 1 Jul 2012
Externally publishedYes

Keywords

  • Fluoroquinolone resistance
  • Gyrase mutations
  • Mycobacterium tuberculosis

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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