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 (π = 0, π = 0.00021, and π = 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.
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 (π = 0, π = 0.00021, and π = 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.
Authors: Alice R Wattam; David Abraham; Oral Dalay; Terry L Disz; Timothy Driscoll; Joseph L Gabbard; Joseph J Gillespie; Roger Gough; Deborah Hix; Ronald Kenyon; Dustin Machi; Chunhong Mao; Eric K Nordberg; Robert Olson; Ross Overbeek; Gordon D Pusch; Maulik Shukla; Julie Schulman; Rick L Stevens; Daniel E Sullivan; Veronika Vonstein; Andrew Warren; Rebecca Will; Meredith J C Wilson; Hyun Seung Yoo; Chengdong Zhang; Yan Zhang; Bruno W Sobral Journal: Nucleic Acids Res Date: 2013-11-12 Impact factor: 16.971
Authors: Qi Wang; Susanna K P Lau; Fei Liu; Yanlin Zhao; Hong Min Li; Bing Xi Li; Yong Liang Hu; Patrick C Y Woo; Cui Hua Liu Journal: PLoS One Date: 2014-10-10 Impact factor: 3.240