耐左氧氟沙星结核分枝杆菌gyrA基因上新的突变位点

New mutations of gyrA gene in levofloxacin-resistant Mycobacterium tuberculosis clinical isolates

目的:分析耐左氧氟沙星结核分枝杆菌临床菌株gyrA基因的突变情况及其耐药机制。方法:用聚合酶链反应(PCR)和DNA直接测序技术(DS)测定64株耐左氧氟沙星结核分枝杆菌gyrA基因的QRDR(quinolone resistance-determining regions)序列。结果:64株耐药菌株有47株QRDR序列发生突变,其中45株为单位点突变,另2株为双位点突变;突变分布为70位突变2株、89位1株、90位12株、91位4株、94位30株,其中70位和89位为新发现的突变位点。结论:结核分枝杆菌喹诺酮类药物耐受现象与gyrA基因QRDR的突变有关,包括新发现的70位和89位突变。

Objective To observe the mutations of gyrA gene in levofloxacin-resistant Mycobactefium Tuberculosis （M.tuberculosis） clinical isolates and study the molecular mechanism of these mutations. Methods Quinolone resistance-determining regions of gyrA gene in sixty-four levofloxacin-resistant M.tuberculosis clinical isolates were analyzed with polymerase chain reaction and DNA direct-sequencing. Results Forty-five of sixty-four clinical isolates mutated in one codon of gyrA gene and two in double codons. Two isolates mutated in codon 70, one in 89, twelve in 90, four in 91, and thirty in 94. Codon 70 and 89 were new mutations. Conclusion Quinolone resistance in most M. tuberculosis is due to the mutations of gyrA gene, including the new mutation in codon 70 and 89.