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

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...

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Vydané v:Journal of antimicrobial chemotherapy Ročník 67; číslo 4; s. 819
Hlavní autori: Maruri, Fernanda, Sterling, Timothy R, Kaiga, Anne W, Blackman, Amondrea, van der Heijden, Yuri F, Mayer, Claudine, Cambau, Emmanuelle, Aubry, Alexandra
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England 01.04.2012
Predmet:
Antitubercular Agents - pharmacology
DNA Gyrase - genetics
DNA Gyrase - metabolism
Drug Resistance, Bacterial
Fluoroquinolones - pharmacology
Humans
Mutation
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - enzymology
Mycobacterium tuberculosis - isolation & purification
Tuberculosis - microbiology
ISSN:1460-2091, 1460-2091
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Shrnutí: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.
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ISSN:1460-2091
1460-2091
DOI:10.1093/jac/dkr566