High proportion of fluoroquinolone-resistant Mycobacterium tuberculosis isolates with novel gyrase polymorphisms and a gyrA region associated with fluoroquinolone susceptibility.

Devasia R, Blackman A, Eden S, Li H, Maruri F, Shintani A, Alexander C, Kaiga A, Stratton CW, Warkentin J, Tang YW, Sterling TR
J Clin Microbiol. 2012 50 (4): 1390-6

PMID: 22189117 · PMCID: PMC3318526 · DOI:10.1128/JCM.05286-11

Fluoroquinolone resistance in Mycobacterium tuberculosis can be conferred by mutations in gyrA or gyrB. The prevalence of resistance mutations outside the quinolone resistance-determining region (QRDR) of gyrA or gyrB is unclear, since such regions are rarely sequenced. M. tuberculosis isolates from 1,111 patients with newly diagnosed culture-confirmed tuberculosis diagnosed in Tennessee from 2002 to 2009 were screened for phenotypic ofloxacin resistance (>2 μg/ml). For each resistant isolate, two ofloxacin-susceptible isolates were selected: one with antecedent fluoroquinolone exposure and one without. The complete gyrA and gyrB genes were sequenced and compared with M. tuberculosis H37Rv. Of 25 ofloxacin-resistant isolates, 11 (44%) did not have previously reported resistance mutations. Of these, 10 had novel polymorphisms: 3 in the QRDR of gyrA, 1 in the QRDR of gyrB, and 6 outside the QRDR of gyrA or gyrB; 1 did not have any gyrase polymorphisms. Polymorphisms in gyrA codons 1 to 73 were more common in fluoroquinolone-susceptible than in fluoroquinolone-resistant strains (20% versus 0%; P = 0.016). In summary, almost half of fluoroquinolone-resistant M. tuberculosis isolates did not have previously described resistance mutations, which has implications for genotypic diagnostic tests.

MeSH Terms (18)

Adult Aged Aged, 80 and over Antitubercular Agents Bacterial Proteins Codon DNA Gyrase DNA Mutational Analysis Drug Resistance, Bacterial Female Fluoroquinolones Humans Male Middle Aged Mutation, Missense Mycobacterium tuberculosis Polymorphism, Genetic Tuberculosis, Pulmonary

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