Plasmid-Mediated Quinolone Resistance

Abstract

Three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998. Plasmid genes qnrA, qnrB, qnrC, qnrD, qnrS, and qnrVC code for proteins of the pentapeptide repeat family that protects DNA gyrase and topoisomerase IV from quinolone inhibition. The qnr genes appear to have been acquired from chromosomal genes in aquatic bacteria, are usually associated with mobilizing or transposable elements on plasmids, and are often incorporated into sul1-type integrons. The second plasmid-mediated mechanism involves acetylation of quinolones with an appropriate amino nitrogen target by a variant of the common aminoglycoside acetyltransferase AAC(6′)-Ib. The third mechanism is enhanced efflux produced by plasmid genes for pumps QepAB and OqxAB. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading. The plasmid-mediated mechanisms provide only low-level resistance that by itself does not exceed the clinical breakpoint for susceptibility but nonetheless facilitates selection of higher-level resistance and makes infection by pathogens containing PMQR harder to treat.

<p>Characterization of Antibiotic-Susceptibility Patterns, Virulence Factor Profiles and Clonal Relatedness in <em>Proteus mirabilis</em> Isolates from Patients with Urinary Tract Infection in Iran</p>

“…We examined the presence of PMQR determinants among the isolates that only qnrA and aac(6ʹ)-Ib-cr genes were detected in the isolates. The resistance mechanisms of fluoroquinolones-resistant isolates in disk diffusion that had none of the PMQR genes could be owing to other mechanisms such as the presence of other qnr genes, changes in DNA gyrase or topoisomerase IV, and efflux systems systems, 45 which were not evaluated in our study. The isolates containing PMQR genes belonged to ESBLs-producing isolates and showed high-level resistance to fluoroquinolones (MIC ≥128 μg/mL for ciprofloxacin and ≥256 μg/mL for norfloxacin), demonstrating the potential of these genes in transferring the resistance to fluoroquinolones among P. mirabilis strains.…”

Identification of a Plasmid‐Mediated Quinolone Resistance Gene in Salmonella Isolates from Texas Dairy Farm Environmental Samples

“…The predominant mechanism of quinolone resistance in Salmonella is the occurrence of topoisomerase mutations; a single point mutation is typically associated with nalidixic acid resistance and intermediate susceptibility to ciprofloxacin, and stepwise mutations further enhance ciprofloxacin resistance (Centers for Disease Control and Prevention (CDC), ). Other mechanisms include expression of plasmid‐mediated resistance genes, such as the qnr genes (protection of target enzyme from quinolone inhibition), qepA gene (quinolone efflux pump), aac(6′)‐Ib‐cr gene (enzymatic modification of some quinolones) and oqxAB genes (multidrug resistance efflux pump) (Jacoby et al., ). Presence of a PMQR gene is generally associated with the discordant pattern of nalidixic acid susceptibility and intermediate susceptibility to ciprofloxacin (Centers for Disease Control and Prevention (CDC), ).…”

“…Presence of a PMQR gene is generally associated with the discordant pattern of nalidixic acid susceptibility and intermediate susceptibility to ciprofloxacin (Centers for Disease Control and Prevention (CDC), ). In the absence of chromosomal mechanisms of quinolone resistance, PMQR genes confer low‐level resistance to ciprofloxacin and may promote clinical resistance to ciprofloxacin (Jacoby et al., ). Furthermore, there is an association between PMQR and multidrug resistance (MDR), as qnr ‐positive plasmids frequently include genes that confer resistance to other anti‐microbial classes (Jacoby et al., ).…”

Konya, Türkiye’de Escherichia coli klinik izolatlarında plazmid aracılı fluorokinolon direnci

“…In the past decade these genes have been found in bacterial isolates from around the world. They reduce the susceptibility of bacteria to quinolones, usually not to the level of nonsusceptibility, but facilitating the selection of more quinolone resistant mutants and treatment failure 6 .…”

“…Hypothesis of plasmid-mediated quinolone resistance (PMQR) was first suggested in a Shigella dysenteriae strain which is resistant to nalidxic acid in 1987; however this hypothesis couldn't be proven 5 . Existance of low level quinolone resistance which was transferable by a plasmid was first shown in Klebsiella pneumoniae strain resistant to ciprofloxacin which was isolated in the urine sample of a patient in 1994 6 .…”