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Chapter 3 : Mechanisms of Quinolone Resistance
Category: Clinical Microbiology
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This chapter reviews the mechanisms of quinolone resistance. Initial studies of resistant clinical isolates of Staphylococcus aureus prior to the recognition of the role of topoisomerase IV in resistance commonly had GyrA mutations, but when ParC and ParE were also evaluated, GyrA quinolone resistance mutations were not found in the absence of mutations in topoisomerase IV. The strongest genetic data for the secondary role of topoisomerase IV in quinolone resistance is from Escherichia coli, in which mutations in ParC or ParE were shown to contribute to resistance only in the presence of mutant GyrA.. The largest body of information concerning the role of topoisomerase IV in quinolone resistance in gram-positive bacteria comes from studies of S. aureus and S. pneumoniae. It seems likely that the role of the Mar and Sox regulons and the AcrAB efflux pump in quinolone resistance in S. enterica serovar Typhimurium will be similar to that in E. coli. Although all four known efflux systems in P. aeruginosa cause increases in resistance to quinolones when overexpressed, quinolone congeners differ in the extent to which they are affected by each system, and use of different quinolones in resistance selections results in differential selection of mutants overexpressing these systems. The two best-studied systems that effect quinolone resistance are NorA of S. aureus and Bmr and Bit of Bacillus subtilis, but additional examples are being identified and studied in other gram-positive bacteria.