Amino acid substitutions at position 95 in GyrA can add fluoroquinolone resistance to Mycobacterium leprae.

Kazumasa Yokoyama, Hyun Kim, Tetsu Mukai, Masanori Matsuoka, Chie Nakajima, Yasuhiko Suzuki

Division of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.

Antimicrobial agents and chemotherapy 2012 Feb

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Amino acid substitutions at position 89 or 91 in GyrA of fluoroquinolone-resistant Mycobacterium leprae clinical isolates have been reported. In contrast, those at position 94 in M. tuberculosis, equivalent to position 95 in M. leprae, have been identified most frequently. To verify the possible contribution of amino acid substitutions at position 95 in M. leprae to fluoroquinolone resistance, we conducted an in vitro assay using wild-type and mutant recombinant DNA gyrases. Fluoroquinolone-mediated supercoiling activity inhibition assay and DNA cleavage assay revealed the potent contribution of an amino acid substitution of Asp to Gly or Asn at position 95 to fluoroquinolone resistance. These results suggested the possible future emergence of quinolone-resistant M. leprae isolates with these amino acid substitutions and the usefulness of detecting these mutations for the rapid identification of fluoroquinolone resistance in leprosy.

Citation

Kazumasa Yokoyama, Hyun Kim, Tetsu Mukai, Masanori Matsuoka, Chie Nakajima, Yasuhiko Suzuki. Amino acid substitutions at position 95 in GyrA can add fluoroquinolone resistance to Mycobacterium leprae. Antimicrobial agents and chemotherapy. 2012 Feb;56(2):697-702