Plasmid-Mediated Quinolone Resistance

Jacoby, George A.; Strahilevitz, Jacob; Hooper, David C.

doi:10.1128/microbiolspec.plas-0006-2013

Cited by 322 publications

(271 citation statements)

References 362 publications

(259 reference statements)

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“…Six types of plasmid-encoded proteins (QnrA, -B, -C, -D, -S, and -VC), are known, some with multiple variants, as well as others encoded on the chromosome especially of aquatic bacteria (3,(10)(11)(12)(13)(14). QnrB variants appear to have the highest prevalence (14). QnrB1 dimerizes via its C-terminal domain to form a rod-like structure that mimics B-form DNA (15).…”

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confidence: 99%

Interactions between QnrB, QnrB Mutants, and DNA Gyrase

Kim

Chen

Braun

et al. 2015

Antimicrob Agents Chemother

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Plasmid-encoded protein QnrB1 protects DNA gyrase from ciprofloxacin inhibition. Using a bacterial two-hybrid system, we evaluated the physical interactions between wild-type and mutant QnrB1, the GyrA and GyrB gyrase subunits, and a GyrBA fusion protein. The interaction of QnrB1 with GyrB and GyrBA was approximately 10-fold higher than that with GyrA, suggesting that domains of GyrB are important for stabilizing QnrB1 interaction with the holoenzyme. Sub-MICs of ciprofloxacin or nalidixic acid reduced the interactions between QnrB1 and GyrA or GyrBA but produced no reduction in the interaction with GyrB or a quinolone-resistant GyrA:S83L (GyrA with S83L substitution) mutant, suggesting that quinolones and QnrB1 compete for binding to gyrase. Of QnrB1 mutants that reduced quinolone resistance, deletions in the C or N terminus of QnrB1 resulted in a marked decrease in interactions with GyrA but limited or no effect on interactions with GyrB and an intermediate effect on interactions with GyrBA. While deletion of loop B and both loops moderately reduced the interaction signal with GyrA, deletion of loop A resulted in only a small reduction in the interaction with GyrB. The loop A deletion also caused a substantial reduction in interaction with GyrBA, with little effect of loop B and dual-loop deletions. Single-amino-acid loop mutations had little effect on physical interactions except for a Δ105I mutant. Therefore, loops A and B may play key roles in the proper positioning of QnrB1 rather than as determinants of the physical interaction of QnrB1 with gyrase.

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confidence: 99%

Interactions between QnrB, QnrB Mutants, and DNA Gyrase

Kim

Chen

Braun

et al. 2015

Antimicrob Agents Chemother

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“…Plasmid-mediated quinolone resistance (PMQR) is conferred by extrinsic resistance determinants that encode efflux pumps (qepA and oqxAB) (8), proteins that protect DNA gyrase and topoisomerase IV through specific binding (qnr genes), or quinolone-inactivating enzymes [aac(6=)-Ib-cr] (9). PMQR genes generally confer low-level resistance, with their MICs falling below Clinical and Laboratory Standards Institute (CLSI) breakpoints for intermediate resistance; therefore, their contribution to quinolone resistance can be masked in strains also harboring QRDR mutations in gyrA and parC.…”

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confidence: 99%

Prevalence of Quinolone Resistance in Enterobacteriaceae from Sierra Leone and the Detection of qnrB Pseudogenes and Modified LexA Binding Sites

Łęski

Stockelman

Bangura³

et al. 2016

Antimicrob Agents Chemother

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A collection of 74 Enterobacteriaceae isolates found in Bo, Sierra Leone, were tested for quinolone antibiotic susceptibility and resistance mechanisms. The majority of isolates (62%) were resistant to quinolones, and 61% harbored chromosomal gyrA and/or parC mutations. Plasmid-mediated quinolone resistance genes were ubiquitous, with qnrB and aac(6=)-Ib-cr being the most prevalent. Mutated LexA binding sites were found in all qnrB1 genes, and truncated qnrB pseudogenes were found in the majority of Citrobacter isolates.

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“…33,34 PMQR determinants are considered to play an important role in the acquisition of high-level fluoroquinolone resistance by selecting for mutants in gyrA and parC and/or efflux pump overexpression. 10 In this study, most isolates had high levels of resistance. We are unable to say whether the PMQR genes were acquired at the beginning or the end of this process.…”

Section: Discussionmentioning

confidence: 97%

“…10 PMQR genes have also often been found coexisting on the same plasmid with genes encoding extended-spectrum beta-lactamases (ESBLs) or AmpC, which can then be cotransferred to a recipient. 10,11 The international spread of PMQR determinants has been reported in different species of Enterobacteriaceae. 12 Only a few reports about the prevalence of PMQR genes in Algeria have been published, most concerning sporadic cases.…”

Section: Introductionmentioning

confidence: 99%