[Study on the gene mutation of quinolone-resistant Mycobacterium tuberculosis isolated from Sichuan Province].
OBJECTIVE
To investigate the molecular mechanism of quinolone-resistance of M. tuberculosis and characterize the gene mutation in Sichuan Province.


METHODS
Susceptibility of the clinical isolates to quinolones (ofloxacin, ciprofloxacin and sparfloxacin) was tested by the absolute concentration method. GyrA gene quinolone reasistance-determining region (QRDR) mutations M. tuberculosis were detected with PCR-SSCP and DNA sequencing.


RESULTS
Of 68 clinical isolates of M. tuberculosis, 25 high-resistant, 11 low-resistant and 10 sensitive isolates were noted to have abnormal gyrA SSCP profile and different gyrA sequences from the standard strain H37Rv, and 14 sensitive and 8 low-resistant isolates were found with no mutation of gyrA gene. DNA sequencing unveiled Ser-->Thr mutation at codon 95, Asp-->Gly at codon 94, Ala-->Val at codon 90, and Ala-->Val at codon 83.


CONCLUSIONS
This study confirmed the strong correlation between the quinolone-resistance and the mutation of gyrA gene, which might be a major molecular mechanism of quinolone-resistance in M. tuberculosis. The types of mutations exhibit no difference between Sichuan Province and other areas in China.
Zhao
Ming-cai
MC
Unit of Infection and Immunity, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Bao
Lang
L
Wu
Yue-han
YH
Long
Yang
Y
Zeng
Xian-wu
XW
Zhang
Hui-dong
HD
Xie
Yi-xin
YX
D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology; D006801:Humans; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000235:genetics*; D015242:Ofloxacin / Q000494:pharmacology; D018807:Polymorphism, Single-Stranded Conformational; D015363:Quinolones / Q000494:pharmacology*
D000904:Antibiotics, Antitubercular; D024841:Fluoroquinolones; D015363:Quinolones; D002939:Ciprofloxacin; D015242:Ofloxacin; C061363:sparfloxacin