Quinolone resistance-associated amino acid substitutions affect enzymatic activity of Mycobacterium leprae DNA gyrase

Tomoyuki Yamaguchi, Kazumasa Yokoyama, Chie Nakajima, Yasuhiko Suzuki

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Quinolones are important antimicrobials for treatment of leprosy, a chronic infectious disease caused by Mycobacterium leprae. Although it is well known that mutations in DNA gyrase are responsible for quinolone resistance, the effect of those mutations on the enzymatic activity is yet to be studied in depth. Hence, we conducted in vitro assays to observe supercoiling reactions of wild type and mutated M. leprae DNA gyrases. DNA gyrase with amino acid substitution Ala91Val possessed the highest activity among the mutants. DNA gyrase with Gly89Cys showed the lowest level of activity despite being found in clinical strains, but it super-coiled DNA like the wild type does if applied at a sufficient concentration. In addition, patterns of time-dependent conversion from relaxed circular DNA into supercoiled DNA by DNA gyrases with clinically unreported Asp95Gly and Asp95Asn were observed to be distinct from those by the other DNA gyrases.

Original languageEnglish
Pages (from-to)1343-1347
Number of pages5
JournalBioscience, Biotechnology and Biochemistry
Volume81
Issue number7
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Amino acid substitution
  • DNA gyrase
  • Enzymatic activity
  • Mycobacterium leprae
  • Quinolone resistance

ASJC Scopus subject areas

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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