A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system

作者：Maruri Fernanda; Sterling Timothy R^*; Kaiga Anne W; Blackman Amondrea; van der Heijden Yuri F; Mayer Claudine; Cambau Emmanuelle; Aubry Alexandra

来源：Journal of Antimicrobial Chemotherapy, 2012, 67(4): 819-831.

DOI：10.1093/jac/dkr566

• gyrA
• gyrB
• QRDRs
• M
• tuberculosis

Fluoroquinolone resistance in Mycobacterium tuberculosis has become increasingly important. A review of mutations in DNA gyrase, the fluoroquinolone target, is needed to improve the molecular detection of resistance. We performed a systematic review of studies reporting mutations in DNA gyrase genes in clinical M. tuberculosis isolates. From 42 studies that met inclusion criteria, 1220 fluoroquinolone-resistant M. tuberculosis isolates underwent sequencing of the quinolone resistance-determining region (QRDR) of gyrA; 780 (64) had mutations. The QRDR of gyrB was sequenced in 534 resistant isolates; 17 (3) had mutations. Mutations at gyrA codons 90, 91 or 94 were present in 654/1220 (54) resistant isolates. Four different GyrB numbering systems were reported, resulting in mutation location discrepancies. We propose a consensus numbering system. Most fluoroquinolone-resistant M. tuberculosis isolates had mutations in DNA gyrase, but a substantial proportion did not. The proposed consensus numbering system can improve molecular detection of resistance and identification of novel mutations.

• 出版日期2012-4