Induction of mycobacterial resistance to quinolone class antimicrobials.

Antimicrobial Agents and Chemotherapy
Muhammad MalikKarl Drlica

Abstract

An agar plate assay was developed for detecting the induction of drug-resistant mycobacterial mutants during exposure to inhibitors of DNA gyrase. When Mycobacterium smegmatis on drug-containing agar, resistant colonies arose over a period of 2 weeks. A recA deficiency reduced mutant recovery, consistent with involvement of the SOS response in mutant induction. The C-8-methoxy compounds gatifloxacin and moxifloxacin allowed the recovery of fewer resistant mutants than either ciprofloxacin or levofloxacin when present at the same multiple of the MIC; a quinolone-like 8-methoxy-quinazoline-2,4-dione was more effective at restricting the emergence of resistant mutants than its cognate fluoroquinolone. Thus, the structure of fluoroquinolone-like compounds affects mutant recovery. A spontaneous mutator mutant of M. smegmatis, obtained by growth in medium containing both isoniazid and rifampin, increased mutant induction during exposure to ciprofloxacin. Moreover, the mutator increased the size of spontaneous resistant mutant subpopulations, as detected by population analysis. Induction of ciprofloxacin resistance was also observed with Mycobacterium tuberculosis H37Rv. When measured with clinical isolates, no difference in mutant re...Continue Reading

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Citations

Sep 28, 2013·The Journal of Antimicrobial Chemotherapy·M McGrathD F Warner
Apr 1, 2017·Microbiology Spectrum·Zanele DitseDigby F Warner
Sep 16, 2021·Microbiology Spectrum·William M MaternPetros C Karakousis

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