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      Mechanisms of drug resistance: quinolone resistance.

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          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.

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          Author and article information

          Journal
          Ann. N. Y. Acad. Sci.
          Annals of the New York Academy of Sciences
          1749-6632
          0077-8923
          Sep 2015
          : 1354
          Affiliations
          [1 ] Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts.
          [2 ] Harvard Medical School, Boston, Massachusetts.
          [3 ] Lahey Hospital and Medical Center, Burlington, Massachusetts.
          Article
          NIHMS699191
          10.1111/nyas.12830
          4626314
          26190223
          © 2015 New York Academy of Sciences.

          topoisomerase, quinolone, plasmids, efflux pumps, DNA gyrase

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