School of Public, Tongji Medical College, Huazhong University of Science and Technology, Ministry of Education Key Laboratory of Environment and Health, Wuhan, China.
Braz J Infect Dis. 2012 Mar-Apr;16(2):136-41. doi: 10.1016/s1413-8670(12)70294-5.
The study aimed to investigate gyrA and gyrB mutations in Mycobacterium tuberculosis (MTB) clinical strains from 93 patients with pulmonary tuberculosis in Hubei Province, China, and analyze the association between mutation patterns of the genes and ofloxacin resistance level.
Among 93 MTB clinical isolates, 61 were ofloxacin-resistant by the proportion method, and 32 were ofloxacin-susceptible MDR-TB. No mutation in the gyrB gene was found in any MTB strains. In the 61 ofloxacin-resistant isolates, 54 mutations were observed in the gyrA gene. Only one mutation in the gyrA gene was found in ofloxacin-susceptible MDR-TB isolates. In this study, the mutation patterns of gyrA involved seven patterns of single codon mutation (A90V, S91P, S91T, D94N, D94Y, D94G or D94A) and two patterns of double codons mutation (S91P & D94H, S91P & D94A). The ofloxacin minimal inhibitory concentrations (MICs) of three patterns of single codon mutations in the gyrA gene (codons 94, 90 and 91) showed a statistically significant difference (p < 0.0001).
The gyrA mutations at codons 90, 91 and 94 constitute the primary mechanism of fluoroquinolone resistance in MTB, and mutations at codon 91 in the gyrA gene may be associated with low-level resistance to ofloxacin.
本研究旨在调查中国湖北省 93 例肺结核患者的结核分枝杆菌（MTB）临床株中 gyrA 和 gyrB 基因突变，并分析基因突变模式与氧氟沙星耐药水平之间的关系。
93 株 MTB 临床分离株中，61 株采用比例法检测为氧氟沙星耐药，32 株为氧氟沙星敏感的耐多药结核病（MDR-TB）。任何 MTB 株均未发现 gyrB 基因突变。在 61 株氧氟沙星耐药分离株中，gyrA 基因观察到 54 个突变。在氧氟沙星敏感的 MDR-TB 分离株中仅发现 1 个 gyrA 基因突变。在本研究中，gyrA 基因突变模式涉及 7 种单密码子突变模式（A90V、S91P、S91T、D94N、D94Y、D94G 或 D94A）和 2 种双密码子突变模式（S91P 和 D94H、S91P 和 D94A）。gyrA 基因中三个单密码子突变（密码子 94、90 和 91）的氧氟沙星最小抑菌浓度（MIC）有统计学显著差异（p<0.0001）。
gyrA 基因在密码子 90、91 和 94 处的突变构成 MTB 氟喹诺酮耐药的主要机制，gyrA 基因密码子 91 处的突变可能与氧氟沙星低度耐药有关。
