Induction of Mycobacterial Resistance to Quinolone Class Antimicrobials

Muhammad Malik; Kalyan Chavda; Xilin Zhao; Nirali Shah; Syed Hussain; Natalia Kurepina; Barry N. Kreiswirth; Robert J. Kerns; Karl Drlica

doi:10.1128/AAC.00474-12

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Induction of Mycobacterial Resistance to Quinolone Class Antimicrobials

Journal article

Open access

Peer reviewed

Induction of Mycobacterial Resistance to Quinolone Class Antimicrobials

Muhammad Malik, Kalyan Chavda, Xilin Zhao, Nirali Shah, Syed Hussain, Natalia Kurepina, Barry N. Kreiswirth, Robert J. Kerns and Karl Drlica

Antimicrobial agents and chemotherapy, Vol.56(7), pp.3879-3887

07/01/2012

DOI: 10.1128/AAC.00474-12

PMCID: PMC3393424

PMID: 22564842

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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 recovery was observed between multidrug-resistant (MDR) and pansusceptible isolates. This finding is consistent with at least some MDR isolates of M. tuberculosis lacking mutators detectable by the agar plate assay. Collectively, the data indicate that the use of fluoroquinolones against tuberculosis may induce resistance and that the choice of quinolone may be important for restricting the recovery of induced mutants.

Microbiology

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Science & Technology

Details

Title: Subtitle: Induction of Mycobacterial Resistance to Quinolone Class Antimicrobials
Creators: Muhammad Malik - Rutgers University–Newark
Kalyan Chavda - Rutgers University–Newark
Xilin Zhao - Rutgers, The State University of New Jersey
Nirali Shah - Rutgers University–Newark
Syed Hussain - Rutgers University–Newark
Natalia Kurepina - Rutgers University–Newark
Barry N. Kreiswirth - Rutgers University–Newark
Robert J. Kerns - University of Iowa
Karl Drlica - Rutgers, The State University of New Jersey
Resource Type: Journal article
Publication Details: Antimicrobial agents and chemotherapy, Vol.56(7), pp.3879-3887
DOI: 10.1128/AAC.00474-12
PMID: 22564842
PMCID: PMC3393424
NLM abbreviation: Antimicrob Agents Chemother
ISSN: 0066-4804
eISSN: 1098-6596
Publisher: Amer Soc Microbiology
Number of pages: 9
Grant note: R01AI073491 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) AI73491; AI087671 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Language: English
Date published: 07/01/2012
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
Record Identifier: 9984365885802771

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