Analysis of mutations in the gyrA and gyrB genes and their association with the resistance of Mycobacterium tuberculosis to levofloxacin, moxifloxacin and gatifloxacin
- 1 January 2013
- journal article
- Published by Microbiology Society in Journal of Medical Microbiology
- Vol. 62 (1), 108-113
- https://doi.org/10.1099/jmm.0.046821-0
Abstract
The purpose of the present study was to analyse mutations in the gyrA and gyrB genes of Mycobacterium tuberculosis and define the possible correlation between these mutations and resistance to levofloxacin (LVX), moxifloxacin (MFX) and gatifloxacin (GAT), based on their MICs. One hundred and forty-two M. tuberculosis clinical isolates were collected from pulmonary tuberculosis patients in the Moscow region. All M. tuberculosis strains were tested for drug susceptibility to rifampicin and isoniazid using the BACTEC MGIT 960 System and to ofloxacin (OFX) using the absolute concentration method on solid Lowenstein–Jensen slants. All in all, 68 strains were selected at random (38 strains were resistant and 30 were susceptible to OFX) for further analysis using the TB-BIOCHIP-2 test system and DNA sequence analysis. The MICs of LVX, MFX and GAT for selected strains were determined using the BACTEC MGIT 960 System. Mutations in the gyrA gene were observed in 36 out of 38 (94.7 %) OFX-resistant M. tuberculosis strains. Asn538Asp and Asp500His substitutions in the gyrB gene only were found in two (5.3 %) strains. Twenty-nine out of 30 OFX-sensitive M. tuberculosis strains had no mutations in either gene. One (3.3 %) OFX-sensitive M. tuberculosis strain carried an Arg485His substitution in gyrB. The results of our investigation showed that there is no clear correlation between the type of mutation in the genes gyrA and gyrB, and the MIC levels of LVX, MFX and GAT for resistant strains. Mutations in gyrA and Asn538Asp, and Asp500His substitutions in gyrB were associated with cross-resistance of M. tuberculosis to fluoroquinolones. The substitution Arg485His in gyrB does not confer resistance to LVX, MFX and GAT in M. tuberculosis.Keywords
This publication has 24 references indexed in Scilit:
- Gel-based microarrays in clinical diagnostics in RussiaExpert Review of Molecular Diagnostics, 2011
- Incidence of Moxifloxacin Resistance in Clinical Mycobacterium tuberculosis Isolates in Houston, TexasJournal of Clinical Microbiology, 2011
- Impact of the E540V Amino Acid Substitution in GyrB of Mycobacterium tuberculosis on Quinolone ResistanceAntimicrobial Agents and Chemotherapy, 2011
- Association of mutation patterns in gyrA/B genes and ofloxacin resistance levels in Mycobacterium tuberculosisisolates from East China in 2009BMC Infectious Diseases, 2011
- Molecular Characterization of Fluoroquinolone Resistance inMycobacterium tuberculosis: Functional Analysis ofgyrAMutation at Position 74Antimicrobial Agents and Chemotherapy, 2011
- Beijing Genotype of Mycobacterium tuberculosis Is Significantly Associated with High-Level Fluoroquinolone Resistance in VietnamAntimicrobial Agents and Chemotherapy, 2009
- Sequence Analyses of Just Four Genes To Detect Extensively Drug-Resistant Mycobacterium tuberculosis Strains in Multidrug-Resistant Tuberculosis Patients Undergoing TreatmentAntimicrobial Agents and Chemotherapy, 2009
- Detection of mutations in Mycobacterium tuberculosis genome determining resistance to fluoroquinolones by hybridization on biological microchipsBulletin of Experimental Biology and Medicine, 2008
- Functional Analysis of DNA Gyrase Mutant Enzymes Carrying Mutations at Position 88 in the A Subunit Found in Clinical Strains of Mycobacterium tuberculosis Resistant to FluoroquinolonesAntimicrobial Agents and Chemotherapy, 2006
- Stepwise Decrease in Moxifloxacin Susceptibility amongst Clinical Isolates of Multidrug-ResistantMycobacterium tuberculosis:Correlation with Ofloxacin SusceptibilityMicrobial Drug Resistance, 2006