Several prp crystal structures have been solved, but little is known about the. Apr 16, 2002 previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. Widespread use of these agents has contributed to the rise of bacterial quinolone resistance. Identification of plasmidmediated quinolone resistance qnr. 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. Previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. Multiplex pcr for detection of plasmidmediated quinolone. 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. Plasmidmediated quinolone resistance determinants qnra, qnrb, and qnrs among clinical isolates of enterobacteriaceae in a korean hospital. Identification of plasmidmediated quinolone resistance. The bestdescribed form of pmqr is determined by the qnr group of genes. Fluoroquinolone resistance is emerging in gramnegative pathogens worldwide.
This new qnr like determinant, smaqnr, was characterized. 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. Full text detection of chromosomal and plasmidmediated. Overall, our results show that plasmidborne qnrb promotes bacterial mutation and the selection of quinoloneresistant mutants. 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. Plasmidmediated quinolone resistance in salmonella serotypes. The first plasmidmediated quinolone resistanceconferring gene qnr, now named qnra, was first reported in a klebsiella pneumoniae clinical isolate from the usa in 1998. Qnr proteins confer quinolone resistance, and belong to the pentapeptide repeat protein prp family. Transferable plasmid mediated quinolone resistance associated with qnr is now widely distributed in. Since then, qnr alleles have been discovered worldwide in clinical strains of gramnegative bacilli.
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. Plasmidmediated quinolone resistance determinants qnr and. Plasmidmediated quinolone resistance among nontyphi. The quinolone resistance and plasmidmediated quinolone resistance determinants qnrb, qnrs and qnra, aac6ibcr of 85 salmonella isolates from chicken carcasses were investigated in this study. The worldwide emergence of plasmidmediated quinolone. The sos response promotes qnrb quinoloneresistance. Review the worldwide emergence of plasmidmediated quinolone. Frequent detection of plasmidmediated quinolone resistance. To the best of our knowledge, there has been no report so far on the frequency of qnr genes among e. Here, we describe the characterization of the qnrb2 promoter and the identification of a lexa.
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 quinolone modifying enzyme, and 3 genes encoding quinolone efflux pumps. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except s. The first plasmidmediated quinolone resistance pmqr deter minant, qnr later termed qnra, was described in a klebsiella pneumoniae. Pdf plasmidmediated quinolone resistance determinants. Quinolones are potent antibacterial agents that specifically target bacterial dna gyrase and topoisomerase iv. Smqnr is clearly capable of decreasing quinolone and. Ofloxacin resistance conferred by qnrs gene encoded on.
As a matter of fact, plasmidencoded, quinolone resistance qnr genes originated in the chromosome of aquatic bacteria. Broad dissemination of plasmidmediated quinolone resistance. Plasmidmediated quinolone resistance in salmonella. Three families of qnr determinants qnra, b and s have been described, but little is known about their expression and regulation. Molecular detection and association of qnra, qnrb, qnrs. Sixteen percent of those isolates carried qnr genes encoding the qnrb1, qnrb2, qnra6 or qnrs1. 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. In 1998, the first tmqr was soundly described, that is, qnra. 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. 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. Quinolone and fluoroquinolone antibiotics are potent, broadspectrum agents commonly used to treat a range of infections. The first factor is a gyrase and also topoisomerasebinding protein, termed qnr, that are members of the larger. Qnr proteins are spread among clinical isolates and contribute to quinolone resistance.
Sma qnr, a new chromosomeencoded quinolone resistance. High prevalence of plasmidmediated quinolone resistance. Identification of plasmidmediated quinolone resistance qnr genes in multidrugresistant gramnegative bacteria from hospital wastewaters and receiving waters in the jinan area, china. 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. Recently, a multiresistance plasmid was discovered that encodes transferable resistance to quinolones. The worldwide emergence of plasmidmediated quinolone resistance. Distribution of quinolone resistance gene qnr in esbl producing. Global fluoroquinolone resistance epidemiology and. Qnr genes are known to confer a lowlevel resistance to fluoroquinolone in enterobacteriaceae. We investigated their prevalence and significance in clinical enterobacteriaceae bacteremic isolates in hong kong. 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.
Resistance to quinolones has been a problem ever since nalidixic acid was introduced into clinical medicine 40 years ago. Biotyping using api 20e revealed different biotypes. 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. Genes were identified to variant level by pcr restriction fragment length polymorphism analysis or sequencing. They are often found on the same resistance plasmids as extended spectrum. 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. Distribution of quinolone resistance gene qnrinesblproducing escherichia coli and klebsiella spp. Wed like to understand how you use our websites in order to improve them.
Plasmidmediated quinolone resistance in nontyphi serotypes. The quinolone resistance rates in our study were higher than the reports of yang et al. Genes were identified to variant level by pcr restriction fragment length polymorphism analysis. 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. Frontiers characterization of fluoroquinolone resistance. Quinolone resistance gene qnr, a member of pmqr determinants, was initially discovered in a strain of klebsiella pneumoniae k.
The first plasmidmediated quinolone resistance pmqr determinant, qnr later termed qnra, was described in a klebsiella pneumoniae strain from the usa in 1998. Plasmidmediated quinoloneresistance qnr genes in clinical isolates of escherichia coli collected from several hospitals of qazvin and. Distribution of quinolone resistance gene qnr in esbl. The increase in plasmidmediated quinolone resistance among nts isolated from humans in the united states. Two new determinants, qnrc and qnrd, have been found recently. 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. Topoisomerases are a large group of enzymes found in all organisms and are involved in maintaining the topological state of. Research open access distribution of quinolone resistance gene qnrinesblproducing escherichia coli and klebsiella spp. Qnr proteins block quinolone inhibition of dna gyrase and topoisomerase iv. New qnr gene cassettes centers for disease control and. 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. A mutational analysis and molecular dynamics simulation of. The spread of plasmidmediated quinolone resistance determinants qnrlike determinants, aac6.
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. 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. Recently, a multiresistance plasmid was discovered that encodes transferable resistance to. Ibcr gene, first discovered in 2003, which encodes a variant of.
Pdf prevalence of plasmidmediated quinolone resistance. Research article open access a mutational analysis and. Characterization of ciprofloxacin resistance in laboratory. Emerging plasmidmediated quinolone resistance associated with. Detection of qnr variants and presence of class1 integrons. Pdf the aim of this study was to investigate plasmidencoded quinolone resistance determinants qnra, qnrb and qnrs in quinoloneresistant. Generally, three mechanisms of plasmidmediated quinolone resistance have been described. Detection of the plasmidmediated quinolone resistance. Several mechanisms of antibiotic resistance exist and. In this study, for the first time, we described the frequency. The qnr proteins belong to the repeated pentapeptidique. Detection of qnr genes in esbls producing and nonproducing. In addition, plasmidmediated quinolone resistance pmqr determinants have been described, namely qnr genes, aac 6ibcr, and efflux pumps genes qepa, qepa2, and oqxab. 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.
Transcriptomic and genome sequencing analyses showed that qnrb promoted gene abundance near the origin of replication oric. Characterization of plasmidmediated qnra and qnrb genes. Research open access frequency of quinolone resistance. Western algeria and to investigate the presence of qnr genes in a. Among 6,057 isolates, 17 qnrpositive isolates and 1 aac6. Smqnr, a new chromosomecarried quinolone resistance. Several recent studies have indicated that plasmidmediated resistance mechanisms also play a significant role in fluoroquinolone resistance, and its prevalence is increasing worldwide. Mechanism of plasmidmediated quinolone resistance pnas. These genes, likely originating in aquatic organisms, code for pentapeptide repeat proteins.
The prevalence of qnr and qepa genes in 660 escherichia coli isolates was investigated in healthy animals. Overall, our results show that plasmidborne qnrb promotes bacterial mutation and the selection of quinolone resistant mutants. The contribution of these genes to the emergence of quinolone resistance is being actively investigated. Chu, in annual reports in medicinal chemistry, 1998. Topoisomerases are a large group of enzymes found in all organisms and are involved in maintaining the topological state of dna. Here, we show that qnrb increases the bacterial mutation rate. 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. Molecular detection and association of qnra, qnrb, qnrs and. Her research interest is genetic variability of microorganisms, especially bacteria of clinical relevance.
We have cloned the plasmidquinolone resistance gene, termed qnr, and found it in an integronlike environment upstream from qace. The recent discovery of plasmidmediated horizontally transferable genes encoding quinolone resistance might shed light on these phenomena. Jun 18, 2019 qnr genes are known to confer a lowlevel resistance to fluoroquinolone in enterobacteriaceae. It was cloned and sequenced and thought to be involved in the repair of dna damage resulting from quinolone treatment 20. Prevalence of plasmidmediated quinolone resistance. Presence of qnr gene in escherichia coli and klebsiella. Increasingly recognized in enterobacteriaceae, plasmidmediated quinolone resistance is encoded by qnr genes. Transferable mechanisms of quinolone resistance from 1998. Plasmidmediated quinolone resistance qnr genes confer lowlevel resistance but provide background for selection of highlyresistant strains. Mechanisms of resistance to quinolones clinical infectious. This study aimed to detect the presence of qnr genes in esblproducing e.
Ibcrpositive isolate were detected, representing 0. 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. 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. Apart from quinolone resistance resulting from mutations in the structural genes gyra, gyrb, and grla, a novel s. 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. For a time, the greater potency of the fluoroquinolones, compared with that of older quinolones, permitted complacency regarding their use, but successful treatment outcomes led to increased use, which, in turn, led to an escalating rate of resistance. Isolates were serotyped according to the kauffmanwhitele minor scheme, and broth microdilution method was used to determine quinolone resistance. Characterization of plasmidmediated quinolone resistance by the. S is one of many plasmidencoded genes that is known to contribute to ofloxacin. The first report on the transferable, plasmidmediated quinolone resistance determinant qnra1 was in 1998. I sssnn 223322002224466 quinolone resistance qnr genes.
The first report on the transferable, plasmidmediated quinoloneresistance determinant qnra1 was in 1998. 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. Resistance to quinolones can also be mediated by plasmids that produce the qnr protein, which protects the quinolone targets from inhibition. Mechanisms of quinolone action and microbial response. 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. Pdf plasmidmediated quinolone resistance determinants qnra. Plasmidmediated quinolone resistance determinants qnr and aac6. In addition, plasmidmediated quinolone resistance pmqr determinants have been described, namely qnr genes, aac 6ibcr, and efflux pumps genes qepa, qepa2, and oqxab 7.
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