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中国广东省左氧氟沙星耐药结核分枝杆菌临床分离株中 gyrA 和 gyrB 基因突变特征。

Mutation characterization of gyrA and gyrB genes in levofloxacin-resistant Mycobacterium tuberculosis clinical isolates from Guangdong Province in China.

机构信息

Institute for Pulmonary Disease, Guangzhou Chest Hospital, Yuexiu District, Guangzhou City, Guangdong Province, China.

出版信息

J Infect. 2010 Jul;61(2):150-4. doi: 10.1016/j.jinf.2010.05.001. Epub 2010 May 7.

Abstract

OBJECTIVE

Fluoroquinolone (FQ)-resistant Mycobacterium tuberculosis (MTB) clinical isolates have emerged in many areas of the world. The aim of this study was to observe the molecular characterization of gyrA and gyrB genes in FQ-resistant MTB clinical isolates from Guangdong Province in China.

MATERIALS AND METHODS

A total of 62 MTB clinical strains were originally isolated from patients with pulmonary tuberculosis. The phenotype of susceptibility of each strain was determined by the absolute concentration method and the sequences of the QRDR in gyrA and gyrB genes were detected with DNA direct sequencing technique.

RESULTS

44 of 60 (73.3%) levofloxacin-resistant MTB clinical isolates, including 17 of 18 (94.4%) high-level resistant strains and 27 of 42 (64.3%) low-level resistant strains, had mutation in QRDR of gyrA gene. The mutation patterns involved six patterns of single codon mutation (H70R, A90V, S91A, D94G, D94A or D94N) and one pattern of double codons mutation (A90V with D94A). Of 60 levofloxacin-resistant MTB clinical isolates, only one (1.6%) mutated in gyrB gene (T511N).

CONCLUSIONS

These findings confirm that mutations of gyrA codons 90, 91 and 94 constitute the primary mechanism of FQ resistance in MTB. Furthermore, our findings indicate that the regional investigations are necessary for the comprehensive understanding of FQ resistance of MTB.

摘要

目的

氟喹诺酮(FQ)耐药结核分枝杆菌(MTB)临床分离株已在世界许多地区出现。本研究旨在观察中国广东省FQ 耐药 MTB 临床分离株中 gyrA 和 gyrB 基因的分子特征。

材料与方法

共分离自肺结核患者的 62 株 MTB 临床株。采用绝对浓度法测定各菌株的表型药敏性,采用 DNA 直接测序技术检测 gyrA 和 gyrB 基因 QRDR 区的序列。

结果

60 株左氧氟沙星耐药 MTB 临床分离株中,44 株(73.3%)在 gyrA 基因 QRDR 区发生突变,包括 17 株(94.4%)高水平耐药株和 27 株(64.3%)低水平耐药株。突变模式涉及 6 种单密码子突变(H70R、A90V、S91A、D94G、D94A 或 D94N)和 1 种双密码子突变(A90V 与 D94A)。60 株左氧氟沙星耐药 MTB 临床分离株中,仅有 1 株(1.6%)gyrB 基因发生突变(T511N)。

结论

这些发现证实了 gyrA 密码子 90、91 和 94 的突变是 MTB 对 FQ 耐药的主要机制。此外,我们的研究结果表明,进行区域调查对于全面了解 MTB 对 FQ 的耐药性是必要的。

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