Open AccessMechanisms of fluoroquinolone monoresistance in M ycobacterium tuberculosis
Author(s) -
Lu Jie,
Liu Min,
Wang Yufeng,
Pang Yu,
Zhao Zhuo
Publication year - 2014
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/1574-6968.12401
Subject(s) - efflux , dna gyrase , mycobacterium tuberculosis , microbiology and biotechnology , escherichia coli , ofloxacin , tuberculosis , mutation , minimum inhibitory concentration , biology , drug resistance , quinolone , multiple drug resistance , chemistry , genetics , antibiotics , ciprofloxacin , medicine , gene , pathology
The gyrase mutations and efflux pumps confer fluoroquinolones (FQ) resistance in M ycobacterium 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 (MIC ≥ 4 μg mL −1 ). The recombinant E scherichia coli with pstB revealed greatly increased MIC level from < 0.125 μg mL −1 to 2 μg mL −1 . For the two isolates harboring high‐level pstB transcripts, the presence of CCCP reduced LFX resistance to 1.0 μg mL −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 .