| 论文题目: | Genomic sequence based scanning for drug resistance-associated mutations and evolutionary analysis of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis |
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| 作者: | Liu, CH; Li, HM; Lu, N; Wang, Q; Hu, YL; Yang, X; Hu, YF; Woo, PCY; Gao, GF; Zhu, B |
| 联系作者: | Liu, CH |
| 刊物名称: | JOURNAL OF INFECTION |
| 期: | 5 |
| 卷: | 65 |
| 页: | 412-422 |
| 年份: | 2012 |
| 影响因子: | 4.126 |
| 论文下载: | 下载地址 |
| 摘要: | Objective: To better understand the molecular mechanisms and evolution of drug resistance in Mycobacterium tuberculosis (M. tuberculosis), we performed a genomic sequence based scanning of drug resistance-associated loci for multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains. Materials and methods: Forty-five pairs of primers covering known drug resistance-associated loci compiled in the TBDReaMDB database were designed to perform the analysis of drug resistance-associated mutations for 14 M. tuberculosis clinical isolates from TB patients in China. Genetic diversity and evolutionary analysis was done using concatenated nucleotide sequences of drug resistance-associated loci. Results: Forty-four types of mutations were identified in 14 M. tuberculosis clinical isolates. Average nucleotide diversity for drug resistance-associated loci increased in the M. tuberculosis isolates as the drug resistance increased (pi = 0, pi = 0.00021, and pi = 0.00028 for susceptible, MDR, and XDR isolates, respectively). The dN/dS ratios for coding regions of drug resistance-associated genes in MDR and XDR isolates were 2.73 and 1.83, respectively. MDR and XDR isolates were distributed sporadically on different branches in the phylogenetic trees. Conclusions: Our study provides supporting evidence to demonstrate that the MDR- and XDR-M. tuberculosis strains have evolved independently driven by positive selection. (C) 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved. |
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