Abstract
Quinolone resistance in bacterial pathogens has primarily been associated with mutations in the quinolone resistance-determining regions (QRDRs) of bacterial type-II topoisomerases, which are DNA gyrase and topoisomerase IV. Depending on the position and type of the mutation (s) in the QRDRs, bacteria either become partially or completely resistant to quinolone. QRDR mutations have been identified and characterized in Salmonella enterica isolates from around the globe, particularly during the last decade, and efforts have been made to understand the propensity of different serovars to carry such mutations. Because there is currently no thorough analysis of the available literature on QRDR mutations in different Salmonella serovars, this review aims to provide a comprehensive picture of the mutational diversity in QRDRs of Salmonella serovars, summarizing the literature related to both typhoidal and non-typhoidal Salmonella serovars with a special emphasis on recent findings. This review will also discuss plasmid-mediated quinolone-resistance determinants with respect to their additive or synergistic contributions with QRDR mutations in imparting elevated quinolone resistance. Finally, the review will assess the contribution of membrane transporter-mediated quinolone efflux to quinolone resistance in strains carrying QRDR mutations. This information should be helpful to guide the routine surveillance of foodborne Salmonella serovars, especially with respect to their spread across countries, as well as to improve laboratory diagnosis of quinolone-resistant Salmonella strains.
Highlights
The bactericidal mode of action of FQs is through the inhibition of the bacterial DNAsynthesis machinery, by interfering with the type-II topoisomerases DNA gyrase and topoisomerase IV [1]
This review focuses on FQ resistance caused by target-site mutations, i.e., mutations in the quinolone resistance-determining regions (QRDRs; see below) of type-II topoisomerases
Quinolone resistance is centered on a small stretch of amino acid residues, commonly referred to as the quinolone resistance-determining regions (QRDRs), of bacterial DNA gyrase and topoisomerase IV
Summary
‘Quinolones’ are a class of bactericides that include all synthetic drugs containing a quinolone or naphthyridone nucleus [1]. Quinolones exert their antibacterial effect by inhibiting bacterial DNA synthesis. The first synthetic quinolone, nalidixic acid, was introduced in 1962 to treat urinary tract infections [2]. Efforts to develop broad-spectrum antibacterial drugs by modifying nalidixic acid resulted in the introduction of “fluoroquinolones” (FQs) in 1980, which feature a fluorine atom at position C-6 of the quinolone ring [2] (Figure 1). FQs, ciprofloxacin and ofloxacin, are excellent drugs to cure typhoidal and non-typhoidal salmonellosis as well as to clear asymptomatic bacillus carriers of the bacteria [6,7,8]. This review focuses on FQ resistance caused by target-site mutations, i.e., mutations in the quinolone resistance-determining regions (QRDRs; see below) of type-II topoisomerases
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