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Review
. 2015 Sep;1354(1):12-31.
doi: 10.1111/nyas.12830. Epub 2015 Jul 17.

Mechanisms of drug resistance: quinolone resistance

David C Hooper  1   2 , George A Jacoby  3   2
Affiliations
Review

Mechanisms of drug resistance: quinolone resistance

David C Hooper et al. Ann N Y Acad Sci. 2015 Sep.

Abstract

Quinolone antimicrobials are synthetic and widely used in clinical medicine. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes, DNA gyrase and DNA topoisomerase IV, are commonly in a localized domain of the GyrA and ParE subunits of the respective enzymes and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include quinolones as well as other antimicrobials, disinfectants, and dyes. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids can confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is due to Qnr proteins that protect the target enzymes from quinolone action, one mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Thus, the bacterial quinolone resistance armamentarium is large.

Keywords: DNA gyrase; efflux pumps; plasmids; quinolone; topoisomerase.

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Figures

Figure 1
Figure 1
Structure of Streptococcus pneumoniae topoisomerase IV-DNA-moxifloxacin complex. From reference .
Figure 1
Figure 1
Structure of Streptococcus pneumoniae topoisomerase IV-DNA-moxifloxacin complex. From reference .
Figure 2
Figure 2
3-D representation of pentapeptide repeat proteins. (A) MfpA from M. tuberculosis (PDB ID: 2BM6), (B) EfsQnr from E. faecalis (PDB ID: 2W7Z), (C) AhQnr from A. hydrophila (PDB ID: 3PSS) and (D) plasmid-mediated QnrB1 (PDB ID: 2XTW)
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