期刊
JOURNAL OF INFECTION
卷 65, 期 5, 页码 412-422出版社
W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2012.06.007
关键词
Multidrug-resistant tuberculosis (MDR-TB); Extensively drug-resistant tuberculosis (XDR-TB); Drug susceptibility test (DST); Evolutionary analysis
资金
- National Basic Research Program of China (973 Program) [2012CB518700]
- National Natural Science Foundation of China (NSFC) [30700975]
- Knowledge Innovation Program of the Chinese Academy of Sciences [KSCX2-EW-J-6]
- Ministry of Health of the People's Republic of China [2012ZX10005007-011]
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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