gyrA/B fluoroquinolone resistance allele profiles amongst Mycobacterium tuberculosis isolates from mainland China

Abstract

Fluoroquinolones are important second-line drugs for the treatment of tuberculosis. A comprehensive profile of resistance mutation patterns of DNA gyrase, the major target of fluoroquinolones, is crucial for molecular diagnosis of drug resistance and improvement of treatment efficacy. To investigate the mutation types of the genes encoding the A and B subunits of DNA gyrase (gyrA and gyrB, respectively) in ofloxacin- and levofloxacin-resistant Mycobacterium tuberculosis strains prevalent in mainland China, 177 clinical drug-resistant isolates collected by the National Tuberculosis Reference Laboratory of China were analysed. The GyrB single mutations (Glu498 and Gly551) and double mutation (Thr539Asn-Gly551Arg) as well as a GyrA double mutation (Asp94Asn-Gly112His) were reported to be involved in fluoroquinolone resistance for the first time. To simplify quantification of the contribution of each mutation type and mutation site to overall fluoroquinolone resistance, a mathematical method was established by assigning each resistance allele a numerical score between 5 and 50 (the larger the number, the higher the resistance level). The score of double mutants is the sum of the scores for the two single alleles. The double mutation types, including Asn538Ile(GyrB)-Asp94Ala(GyrA), Ala543Val(GyrB)-Asp94Asn(GyrA) and Ala543Val(GyrB)-Asp94Gly(GyrA) scored relatively high by this methodology.