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Microb Drug Resist. 2013 Feb;19(1):15-20. doi: 10.1089/mdr.2012.0090. Epub 2012 Sep 26.

Functional characterization of quinolone-resistant mechanisms in a lab-selected Salmonella enterica typhimurium mutant.

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1
Department of Microbiology, 3201 Hospital, Hanzhong, China.

Abstract

Correlation has been widely accepted between quinolone resistance and topoisomerase point mutations in quinolone resistance determination regions (QRDRs). Acquirement of point mutations in QRDRs usually increases the microbial resistance to both nalidixic acid and fluoroquinolones. The quinolone-resistant mechanisms accumulated in a lab-selected mutant were characterized through the construction of isogenic mutants using phage λ Red recombinase system and phage P22. The function of a quinolone-resistant mechanism that increased resistance to fluoroquinolones, but decreased resistance to nalidixic acid was fully characterized. A previous reported point mutation in ParC (G78D) was identified in the lab-selected mutant LT2-128. Minimal inhibitory concentrations (MICs) of isogenic mutants showed that acquirement of this point mutation in the host with topoisomerase mutations in GyrA could increase 8- to 32-fold fluoroquinolones MICs, but decrease eight-fold nalidixic acid MICs. Multiple-resistant mechanisms, such as the overexpressed effluxes, were accumulated besides the point mutations in QRDRs in LT2-128 during the mutant selection process. Through biological costs comparison among isogenic mutants, we found the biological cost in LT2-128 was not from the mutations in QRDRs, instead it was from other mutations accumulated during the mutant selection process, such as the mechanisms related to constitutively overexpressed effluxes. Mutation in ParC (G78D) was responsible for the increased resistance to fluoroquinolones, but decreased resistance to nalidixic acid. The existence of this mechanism demonstrated mutations in ParC could play different roles in nalidixic acid and ciprofloxacin resistance.

PMID:
23013383
DOI:
10.1089/mdr.2012.0090
[Indexed for MEDLINE]
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