Quinolones are potent antibacterial agents that specifically target bacterial dna gyrase and topoisomerase iv. The first plasmidmediated quinolone resistance pmqr deter minant, qnr later termed qnra, was described in a klebsiella pneumoniae. Identification of plasmidmediated quinolone resistance. Here, we describe the characterization of the qnrb2 promoter and the identification of a lexa. Wed like to understand how you use our websites in order to improve them. Overall, our results show that plasmidborne qnrb promotes bacterial mutation and the selection of quinolone resistant mutants. Their betahelical structure is interrupted by the loop a 8 amino acids and loop b 12 amino acids, this last one with a significant role in quinolone resistance. Plasmidmediated quinoloneresistance qnr genes in clinical isolates of escherichia coli collected from several hospitals of qazvin and. Ibcr and qepa genes was evaluated in a collection of 281 nalidixic acidresistant enterobacterial isolates recovered between september 2005 and december 2007 at the sahloul hospital, sousse, tunisia. Mechanisms of resistance to quinolones clinical infectious. The first report on the transferable, plasmidmediated quinoloneresistance determinant qnra1 was in 1998. Plasmidmediated quinolone resistance determinants qnra, qnrb, and qnrs among clinical isolates of enterobacteriaceae in a korean hospital.
Molecular detection and association of qnra, qnrb, qnrs. Plasmidmediated quinolone resistance in salmonella. The prevalence of qnr and qepa genes in 660 escherichia coli isolates was investigated in healthy animals. Since then, qnr alleles have been discovered worldwide in clinical strains of gramnegative bacilli. Plasmidmediated quinolone resistance qnr genes confer lowlevel resistance but provide background for selection of highlyresistant strains. The first factor is a gyrase and also topoisomerasebinding protein, termed qnr, that are members of the larger. I sssnn 223322002224466 quinolone resistance qnr genes. Global fluoroquinolone resistance epidemiology and. Characterization of plasmidmediated quinolone resistance by the. Fluoroquinolone resistance is emerging in gramnegative pathogens worldwide.
Distribution of quinolone resistance gene qnr in esbl producing. Quinolone resistance gene qnr, a member of pmqr determinants, was initially discovered in a strain of klebsiella pneumoniae k. To the best of our knowledge, there has been no report so far on the frequency of qnr genes among e. Qnr genes are known to confer a lowlevel resistance to fluoroquinolone in enterobacteriaceae. In 1998, the first tmqr was soundly described, that is, qnra. Here we report the cloning of qnr, the novel plasmidencoded quinolone resistance gene, the amplification and purification of qnr, its gene product, and the demonstration that qnr directly protects e.
Recently, a multiresistance plasmid was discovered that encodes transferable resistance to quinolones. Resistance to these agents is multifactorial and can be via one or a combination of targetsite gene mutations, increased production of multidrugresistance mdr efflux pumps, modifying enzymes, andor targetprotection proteins. Emerging plasmidmediated quinolone resistance associated with. Qnr proteins are spread among clinical isolates and contribute to quinolone resistance. High prevalence of plasmidmediated quinolone resistance. Interaction of the plasmidencoded quinolone resistance.
They are often found on the same resistance plasmids as extended spectrum. May 22, 2008 quinolone resistance in enterobacteriaceae results mainly from mutations in type ii dna topoisomerase genes andor changes in the expression of outer membrane and efflux pumps. Transferable plasmid mediated quinolone resistance associated with qnr is now widely distributed in. Increasingly recognized in enterobacteriaceae, plasmidmediated quinolone resistance is encoded by qnr genes. Biotyping using api 20e revealed different biotypes.
Ofloxacin resistance conferred by qnrs gene encoded on. Identification of plasmidmediated quinolone resistance qnr genes in multidrugresistant gramnegative bacteria from hospital wastewaters and receiving waters in the jinan area, china. Pdf prevalence of plasmidmediated quinolone resistance. Nov, 2018 quinolone resistance determining region mutations were characterized, and it was found that gyra mutations occurred in some of the highlevel resistant mutants although qnr was present in both wildtype susceptible and resistant mutant strains. The quinolone resistance rates in our study were higher than the reports of yang et al. Molecular detection and association of qnra, qnrb, qnrs and. Recently, a multiresistance plasmid was discovered that encodes transferable resistance to. Broad dissemination of plasmidmediated quinolone resistance. The traditional understanding that quinolone resistance is acquired only through mutation and transmitted only vertically does not entirely account for the relative ease with which resistance develops in exquisitely susceptible organisms, or for the very strong association between resistance to quinolones and to other. Characterization of plasmidmediated qnra and qnrb genes. Isolates were serotyped according to the kauffmanwhitele minor scheme, and broth microdilution method was used to determine quinolone resistance.
Topoisomerases are a large group of enzymes found in all organisms and are involved in maintaining the topological state of. Pdf the aim of this study was to investigate plasmidencoded quinolone resistance determinants qnra, qnrb and qnrs in quinoloneresistant. The first plasmidmediated quinolone resistance pmqr determinant, qnr later termed qnra, was described in a klebsiella pneumoniae strain from the usa in 1998. Western algeria and to investigate the presence of qnr genes in a. Frequent detection of plasmidmediated quinolone resistance. Quinolone resistance in enterobacteriaceae results mainly from mutations in type ii dna topoisomerase genes andor changes in the expression of outer membrane and efflux pumps. Characterization of ciprofloxacin resistance in laboratory. Her research interest is genetic variability of microorganisms, especially bacteria of clinical relevance. Previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. Detection of the plasmidmediated quinolone resistance.
Two new determinants, qnrc and qnrd, have been found recently. Plasmidmediated quinolone resistance among nontyphi. Plasmidmediated quinolone resistance in nontyphi serotypes. In addition, all resistant or intermediateresistant isolates to either ciprofloxacin or levofloxacin were screened for 5 genes encoding the quinolone resistance protein qnr, 1 gene encoding quinolonemodifying enzyme, and 3 genes encoding quinolone efflux pumps. In this study, for the first time, we described the frequency. Mechanism of plasmidmediated quinolone resistance pnas.
Frontiers characterization of fluoroquinolone resistance. Genes were identified to variant level by pcr restriction fragment length polymorphism analysis. Resistance to quinolones has been a problem ever since nalidixic acid was introduced into clinical medicine 40 years ago. The increase in plasmidmediated quinolone resistance among nts isolated from humans in the united states. Qnr proteins confer quinolone resistance, and belong to the pentapeptide repeat protein prp family. The recent discovery of plasmidmediated horizontally transferable genes encoding quinolone resistance might shed light on these phenomena. Here, we show that qnrb increases the bacterial mutation rate. Plasmidmediated quinolone resistance determinants qnr and. Plasmidmediated quinolone resistance in salmonella serotypes. Research article open access a mutational analysis and. Resistance to these agents is multifactorial and can be via one or a combination of targetsite gene mutations, increased production of multidrug resistance mdr efflux pumps, modifying enzymes, andor targetprotection proteins. Ibcr gene, first discovered in 2003, which encodes a variant of.
Detection of qnr variants and presence of class1 integrons. Distribution of quinolone resistance gene qnr in esbl. Sma qnr, a new chromosomeencoded quinolone resistance. Genes were identified to variant level by pcr restriction fragment length polymorphism analysis or sequencing. As a result, there has been a developing interest on the reservoirs for quinolone resistance genes and on the potential risks associated with the use of these antibiotics in nonclinical environments.
Generally, three mechanisms of plasmidmediated quinolone resistance have been described. In addition, plasmidmediated quinolone resistance pmqr determinants have been described, namely qnr genes, aac 6ibcr, and efflux pumps genes qepa, qepa2, and oqxab 7. Three families of qnr determinants qnra, b and s have been described, but little is known about their expression and regulation. Chu, in annual reports in medicinal chemistry, 1998. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except s. The qnr proteins belong to the repeated pentapeptidique. The contribution of these genes to the emergence of quinolone resistance is being actively investigated. These genes, likely originating in aquatic organisms, code for pentapeptide repeat proteins.
Several recent studies have indicated that plasmidmediated resistance mechanisms also play a significant role in fluoroquinolone resistance, and its prevalence is increasing worldwide. To gain further insights into the role in quinolone resistance of qnr like pentapeptide repeat proteins prps from different species, we carried out an in silico analysis and found that the s. Pdf plasmidmediated quinolone resistance determinants. Nov 22, 20 we investigated the prevalence of plasmidmediated quinolone resistance pmqr qnr genes by the polymerase chain reaction pcr in antibioticresistant bacteria isolates collected from aquatic environments in jinan during 2 years 2008. Apr 16, 2002 previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. A mutational analysis and molecular dynamics simulation of. Presence of qnr gene in escherichia coli and klebsiella. Ibcrpositive isolate were detected, representing 0. Sixteen percent of those isolates carried qnr genes encoding the qnrb1, qnrb2, qnra6 or qnrs1. S is one of many plasmidencoded genes that is known to contribute to ofloxacin. Several mechanisms of antibiotic resistance exist and. Identification of plasmidmediated quinolone resistance qnr.
Pdf plasmidmediated quinolone resistance determinants qnra. Review the worldwide emergence of plasmidmediated quinolone. Full text detection of chromosomal and plasmidmediated. New qnr gene cassettes centers for disease control and. Plasmidmediated quinolone resistance in salmonella serotypes isolated from chicken carcasses in turkey zafer ata 1, artun yibar 2, erdem arslan 3, kaan mustak4, elcin gunaydin5 1military veterinary school and educational central commandership, bursa, turkey 2uludag university, faculty of veterinary medicine, department of food hygiene and technology, 3department of pharmacology and. Smqnr is clearly capable of decreasing quinolone and. In addition, plasmidmediated quinolone resistance pmqr determinants have been described, namely qnr genes, aac 6ibcr, and efflux pumps genes qepa, qepa2, and oqxab. Quinolone resistancedetermining region mutations were characterized, and it was found that gyra mutations occurred in some of the highlevel resistant mutants although qnr was present in both wildtype susceptible and resistant mutant strains. A novel mechanism of plasmidmediated quinolone resistance was recently reported that involves dna gyrase protection by a protein from the pentapeptide repeat family called qnr. The first plasmidmediated quinolone resistanceconferring gene qnr, now named qnra, was first reported in a klebsiella pneumoniae clinical isolate from the usa in 1998. The bestdescribed form of pmqr is determined by the qnr group of genes. Mechanisms of quinolone action and microbial response. Detection of qnr genes in esbls producing and nonproducing. We investigated the prevalence of plasmidmediated quinolone resistance pmqr qnr genes by the polymerase chain reaction pcr in antibioticresistant bacteria isolates collected from aquatic environments in jinan during 2 years 2008.
Resistance to quinolones can also be mediated by plasmids that produce the qnr protein, which protects the quinolone targets from inhibition. Distribution of quinolone resistance gene qnrinesblproducing escherichia coli and klebsiella spp. Smqnr, a new chromosomecarried quinolone resistance. We investigated their prevalence and significance in clinical enterobacteriaceae bacteremic isolates in hong kong. Overall, our results show that plasmidborne qnrb promotes bacterial mutation and the selection of quinoloneresistant mutants. Widespread use of these agents has contributed to the rise of bacterial quinolone resistance.
These genes, likely originating in aquatic organisms, code for. Multiplex pcr for detection of plasmidmediated quinolone. The worldwide emergence of plasmidmediated quinolone resistance. It was cloned and sequenced and thought to be involved in the repair of dna damage resulting from quinolone treatment 20. This new qnr like determinant, smaqnr, was characterized. The sos response promotes qnrb quinoloneresistance. Summary although plasmidmediated quinolone resistance pmqr was thought not to exist before its discovery in 1998, the past decade has seen an explosion of research characterizing this phenomenon. Prevalence of plasmidmediated quinolone resistance. The spread of plasmidmediated quinolone resistance determinants qnrlike determinants, aac6. The worldwide emergence of plasmidmediated quinolone. Research open access distribution of quinolone resistance gene qnrinesblproducing escherichia coli and klebsiella spp.
Here, we report the presence of qnr variants in human isolates of nontyphi serotypes of salmonella enterica hereafter referred to as nontyphi salmonella from the united states national antimicrobial resistance monitoring system for. This paper on the fluoroquinolone resistance epidemiology stratifies the data according to the different prescription patterns by either primary or tertiary caregivers and by indication. Research open access frequency of quinolone resistance. We have cloned the plasmidquinolone resistance gene, termed qnr, and found it in an integronlike environment upstream from qace. Several prp crystal structures have been solved, but little is known about the. Transferable mechanisms of quinolone resistance from 1998.
Accordingly, the phenomenon of plasmidmediated quinolone resistance is being closely evaluated. Among 6,057 isolates, 17 qnrpositive isolates and 1 aac6. This study aimed to detect the presence of qnr genes in esblproducing e. Results qnrb increases the bacterial mutation rate previous studies showed that, in the presence of qnr genes, a variety of mutations are selected to enhance. Transcriptomic and genome sequencing analyses showed that qnrb promoted gene abundance near the origin of replication oric. Quinolone and fluoroquinolone antibiotics are potent, broadspectrum agents commonly used to treat a range of infections. Nov 25, 2019 in addition, plasmidmediated quinolone resistance pmqr determinants have been described, namely qnr genes, aac 6ibcr, and efflux pumps genes qepa, qepa2, and oqxab. While the description of resistance to quinolones is almost as old as these antimicrobial agents themselves, transferable mechanisms of quinolone resistance tmqr remained absent from the scenario for more than 36 years, appearing first as sporadic events and afterward as epidemics. Qnr proteins block quinolone inhibition of dna gyrase and topoisomerase iv. Topoisomerases are a large group of enzymes found in all organisms and are involved in maintaining the topological state of dna. Although plasmidmediated quinolone resistance pmqr was thought not to exist before its discovery in 1998, the past decade has seen an explosion of research characterizing this phenomenon. Plasmidmediated quinolone resistance determinants qnr and aac6. The first report on the transferable, plasmidmediated quinolone resistance determinant qnra1 was in 1998. This suggests a possible enrichment of plasmidmediated quinolone resistance in the activated sludge p quinolone resistance was recently reported that involves dna gyrase protection by a protein from the pentapeptide repeat family called qnr.