Comparison of gyrA gene mutations between laboratory-selected ofloxacin-resistant Mycobacterium tuberculosis strains and clinical isolates

A Systematic Review Of Gyrase Mutations Associated With Fluoroquinolone-Resistant Mycobacterium Tuberculosis And A Proposed Gyrase Numbering System

“…Other, more rapid testing methods included multiplex allele-specific PCR (MAS-PCR), 53 PCR single-stranded conformation polymorphism/multiplex PCR amplimer conformation (PCR-SSCP/MPAC), 54 pyrosequencing, 55 denaturing HPLC (DHPLC), 47 non-radioactive PCR-SSCP, 3,8,41 locked nucleic acid probe real-time PCR (LNA-PCR) 48 and Table 2. a Some studies that sequenced the QRDR of gyrA also included some codons near the QRDR, but not the entire gyrA.…”

“…37 b Substitutions Ala74Ser and Ala90Gly were never observed independently. 18,26,33,46,47 Systematic review 825 JAC an error in the molecular detection of resistance or the presence of a mixture of strains. For example, in a specimen that harbours mutations leading to GyrA Ala90Val, Asp94Ala and wild-type alleles, results of phenotypic susceptibility testing may have reflected only the wild-type strain.…”

“…c Substitutions GyrA Ala74Ser and Ala90Gly, and GyrB Gly470Ala, Asn499Lys and D644-645 were never observed independently. 18,21,26,33,42,46,47 Systematic review 827 JAC …”

Role of fluoroquinolones in the treatment of tuberculosis

“…The presence of missense mutations in the so-called quinolone resistance-determining region (QRDR) of gyrA or gyrB genes conferring resistance to FQs was subsequently confirmed by using clinical M. tuberculosis isolates in multiple studies [83][84][85][87][88][89][90][91][92][93][94][95][96][97]. The presence of S95 or T95 at gyrA codon 95 is a naturally occurring polymorphism that is not associated with resistance of M. tuberculosis isolates to FQs.…”

“…However, this polymorphism together with katG codon 463 polymorphism (R463 or L463), is used to define the three principal genetic groups of worldwide collection of M. tuberculosis strains [98][99][100]. The FQ-resistant clinical M. tuberculosis isolates more frequently contain mutations in gyrA gene, particularly at codon 90 (A90) or codon 94 (D94) but also occasionally at codon 74 (A74), codon 88 (G88) and codon 91 (S91) while mutations in few codons of the gyrB gene occur in a small minority of clinical strains [83,[89][90][91]. Surprisingly, some M. tuberculosis isolates have also been described that are hypersusceptible to FQs due to mutations at gyrA codon 80 (T80), particularly in association with other FQ resistance-associated mutations [83].…”