The gyrase mutations and efflux pumps confer fluoroquinolones (FQ) resistance in Mycobacterium tuberculosis. However, the contribution of two mechanisms in FQ mono-resistant M.tuberculosis is still unclear. Here, we investigated the contribution of gyrase mutations and efflux pumps to FQ resistance among 17 clinical FQ mono-resistant strains. Our data showed that gyrase mutations in gyrA QRDR were only responsible for four FQ mono-resistant strains. Mutations located in Ala90 and Asp94 of GyrA confer high-level LFX resistance, which can be explained by 3D modeling affinity change between GyrA and LFX. In addition, we found that a high level of efflux pump pstB transcripts may confer FQ resistance in two high-level FQ-resistant isolates (MIC4gmL(-1)). The recombinant Escherichia coli with pstB revealed greatly increased MIC level from <0.125gmL(-1) to 2gmL(-1). For the two isolates harboring high-level pstB transcripts, the presence of CCCP reduced LFX resistance to 1.0gmL(-1). The transcriptional levels of pstB showed no significant difference among 10 clinical M.tuberculosis isolates with different drug susceptibility profiles. In conclusion, our findings demonstrate that both QRDR mutation and efflux pump mechanisms are responsible for monoresistance to FQ. PstB may serve as FQ-related efflux pumps in M.tuberculosis.
基金：
National Grant Research Program of China [2012ZX10004209]
第一作者机构：[1]Capital Med Univ, Beijing Childrens Hosp, Beijing Pediat Res Inst, Beijing Key Lab Pediat Dis Otolaryngol Head & Nec, Beijing, Peoples R China;[2]Chinese Ctr Dis Control & Prevent, Natl Ctr TB Control & Prevent, Beijing, Peoples R China;
通讯作者：
通讯机构：[3]Liaoning Prov Ctr Dis Control & Prevent, Shenyang 110005, Peoples R China;[4]Liaoning Prov Ctr Dis Control & Prevent, 242 Shayang Rd, Shenyang 110005, Peoples R China
推荐引用方式(GB/T 7714)：
Lu Jie,Liu Min,Wang Yufeng,et al.Mechanisms of fluoroquinolone monoresistance in Mycobacterium tuberculosis[J].FEMS MICROBIOLOGY LETTERS.2014,353(1):40-48.doi:10.1111/1574-6968.12401.
APA：
Lu, Jie,Liu, Min,Wang, Yufeng,Pang, Yu&Zhao, Zhuo.(2014).Mechanisms of fluoroquinolone monoresistance in Mycobacterium tuberculosis.FEMS MICROBIOLOGY LETTERS,353,(1)
MLA：
Lu, Jie,et al."Mechanisms of fluoroquinolone monoresistance in Mycobacterium tuberculosis".FEMS MICROBIOLOGY LETTERS 353..1(2014):40-48
