A newly identified 191A/C mutation in the Rv2629 gene that was significantly associated with rifampin resistance in Mycobacterium tuberculosis.
In an effort to identify the new resistance factors in rifampin resistant (RIF (r)) Mycobacterium tuberculosis ( M. tb), comparative proteome analysis and gene mutation assays were used to identify the differentially expressed proteins and correlated gene mutations among clinical RIF (r) isolates lacking rpoB mutations, RIF sensitive (RIF (s)) isolates, and the laboratory H37Rv strain. MALDI-TOF-MS revealed nine differentially expressed protein spots. PCR sequencing results showed four genes were mutated. The newly identified 191A/C mutation, in the gene Rv2629, was carried by 111 out of 112 clinical RIF (r) isolates. However, this mutation was absent in H37Rv and RIF (s) isolates. The RIF (s) species Mycobacterium smegmatis displayed RIF resistance only after being transformed with the mutated M. tb Rv2629, while it was not restored by the wild type gene. These results indicate that the 191A/C mutation of the Rv2629 gene may be associated with RIF resistance.
Wang
Qingzhong
Q
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University and Shanghai Pneumology Hospital, Shanghai, PRC.
Yue
Jun
J
Zhang
Lu
L
Xu
Ying
Y
Chen
Jiazhen
J
Zhang
Min
M
Zhu
Bingdong
B
Wang
Hongyan
H
Wang
Honghai
H
D000225:Adenine; D000595:Amino Acid Sequence; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D003596:Cytosine; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D017354:Point Mutation; D012293:Rifampin / Q000494:pharmacology*
D000904:Antibiotics, Antitubercular; D001426:Bacterial Proteins; C527629:Rv2629 protein, Mycobacterium; D003596:Cytosine; D000225:Adenine; D012293:Rifampin