Interaction of plasmid and host quinolone resistance (original) (raw)
Related papers
Mechanism of plasmid-mediated quinolone resistance
Proceedings of The National Academy of Sciences, 2002
Quinolones are potent antibacterial agents that specifically target bacterial DNA gyrase and topoisomerase IV. Widespread use of these agents has contributed to the rise of bacterial quinolone resistance. Previous studies have shown that quinolone resistance arises by mutations in chromosomal genes. Recently, a multiresistance plasmid was discovered that encodes transferable resistance to quinolones. We have cloned the plasmid-quinolone resistance gene, termed qnr, and found it in an integron-like environment upstream from qacE⌬1 and sulI. The gene product Qnr was a 218-aa protein belonging to the pentapeptide repeat family and shared sequence homology with the immunity protein McbG, which is thought to protect DNA gyrase from the action of microcin B17. Qnr had pentapeptide repeat domains of 11 and 28 tandem copies, separated by a single glycine with a consensus sequence of A͞C D͞N L͞F X X. Because the primary target of quinolones is DNA gyrase in Gram-negative strains, we tested the ability of Qnr to reverse the inhibition of gyrase activity by quinolones. Purified Qnr-His6 protected Escherichia coli DNA gyrase from inhibition by ciprofloxacin. Gyrase protection was proportional to the concentration of Qnr-His6 and inversely proportional to the concentration of ciprofloxacin. The protective activity of Qnr-His6 was lost by boiling the protein and involved neither quinolone inactivation nor independent gyrase activity. Protection of topoisomerase IV, a secondary target of quinolone action in E. coli, was not evident. How Qnr protects DNA gyrase and the prevalence of this resistance mechanism in clinical isolates remains to be determined.
Interaction of the Plasmid-Encoded Quinolone Resistance Protein Qnr with Escherichia coli DNA Gyrase
Antimicrobial Agents and Chemotherapy, 2005
Updated information and services can be found at: These include: REFERENCES http://aac.asm.org/content/49/1/118#ref-list-1 at: This article cites 40 articles, 21 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders:
Quinolone resistance from a transferable plasmid
Lancet, 1998
Background Bacteria can mutate to acquire quinolone resistance by target alterations or diminished drug accumulation. Plasmid-mediated resistance to quinolones in clinical isolates has been claimed but not confirmed. We investigated whether a multiresistance plasmid could transfer resistance to quinolones between bacteria.
Plasmid-Mediated Quinolone Resistance in Clinical Isolates of Escherichia coli from Shanghai, China
Antimicrobial Agents and Chemotherapy, 2003
from Escherichia coli Clinical Isolates of Plasmid-Mediated Quinolone Resistance in http://aac.asm.org/content/47/7/2242 Updated information and services can be found at: These include: REFERENCES http://aac.asm.org/content/47/7/2242#ref-list-1 at: This article cites 25 articles, 15 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders:
2017
Purpose. The aim of the study was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) genes in an unselected collection of bloodstream isolates recovered over an 18-month period in a laboratory affiliated to a university hospital in Athens, Greece, and to assess their impact on the in vitro activity of ciprofloxacin and levofloxacin. Methods. Eight PMQR genes were screened by PCR and sequencing. All PMQR-positive isolates were submitted to isoelectric focusing for b-lactamase detection, conjugation or transformation, time-kill assays, mutant prevention concentrationand inoculum effect evaluation. PCR and sequencing of gyrA and parC were performed for detection of chromosomal mutations. Results. Among 96 Gram-negative isolates, 7 (7.3 %) carried one or more PMQR genes. qnrS1 was the most prevalent (5.2 %), followed by aac(6¢)-Ib-cr (4.2 %) and their combination (2 %). Cloning was successful for three isolates. The presence of a single PMQR determinant without any target modification was not associated with quinolone resistance with one exception, Stenotrophomonas maltophilia carrying qnrS1, which was resistant to norfloxacin and ciprofloxacin, but in this isolate, additional mechanisms of quinolone resistance cannot be excluded. All PMQR-positive isolates showed a significant inoculum effect. The mutant prevention concentrations of ciprofloxacin against the quinolone-susceptible clinical isolates ranged from 0.38 to 32 mg l À1 and those of levofloxacin from 1 to 32 mg l À1. Conclusions. PMQRs compromised the bactericidal activity of ciprofloxacin and levofloxacin when expressed in Enterobacter cloacae, S. maltophilia or Klebsiella pneumoniae and when more than one co-existed. PMQR determinants represent an unrecognized threat, capable to compromise the in vitro activity of quinolones if expressed in a favourable genetic environment and to favour selection of resistant mutants by widening the mutant selection window of these agents.
Plasmid-mediated quinolone resistance: Two decades on
Drug Resistance Updates, 2016
After two decades of the discovery of plasmid-mediated quinolone resistance (PMQR), three different mechanisms have been associated to this phenomenon: target protection (Qnr proteins, including several families with multiple alleles), active efflux pumps (mainly QepA and OqxAB pumps) and drug modification [AAC(6)-Ib-cr acetyltransferase]. PMQR genes are usually associated with mobile or transposable elements on plasmids, and, in the case of qnr genes, are often incorporated into sul1-type integrons. PMQR has been found in clinical and environmental isolates around the world and appears to be spreading. Although the three PMQR mechanisms alone cause only low-level resistance to quinolones, they can complement other mechanisms of chromosomal resistance to reach clinical resistance level and facilitate the selection of higher-level resistance, raising a threat to the treatment of infections by microorganisms that host these mechanisms.
Antimicrobial Agents and Chemotherapy, 2019
In a previous study, mutants with enhanced ciprofloxacin resistance were selected from E. coli J53 pMG252 carrying qnrA1. Strain CipR 8-2 showed an increase in the copy number and transcription level of qnrA1. We sequenced the plasmids on Illumina and MinION platforms. Parental plasmid pMG252 and plasmid pMG252A from strain 8-2 were almost identical except for the region containing qnrA1 that in pMG252A contained 4 additional copies of the qnrA1-qacEΔ1-sul1-ISCR1 region.
Antimicrobial Agents and Chemotherapy, 2019
In a previous study, mutants with enhanced ciprofloxacin resistance (Cip r) were selected from Escherichia coli J53/pMG252 carrying qnrA1. Strain J53 Cip r 8-2 showed an increase in the copy number and transcription level of qnrA1. We sequenced the plasmids on Illumina and MinION platforms. Parental plasmid pMG252 and plasmid pMG252A from strain J53 Cip r 8-2 were almost identical, except for the region containing qnrA1 that in pMG252A contained 4 additional copies of the qnrA1-qacEΔ1-sul1-ISCR1 region. KEYWORDS A/C 2 plasmid, Escherichia coli, ISCR1, ciprofloxacin, qnrA1
Journal of Antimicrobial Chemotherapy, 2009
Pentapeptide repeat proteins (PRPs) QnrA, QnrB and QnrS confer reduced susceptibility to quinolones. This study presents an in vitro analysis of the genetic evolution of quinolone resistance mediated by changes in the coding sequences and promoter regions of qnrA1, qnrS1 and qnrB1 genes. Methods: A random mutagenesis technique was used to predict the evolutionary potential of these PRPs against nalidixic acid and fluoroquinolones. After comparing the amino acid sequences of these and other PRPs protecting bacteria from quinolone activity, several conserved positions were found. The role of these residues in their effect against quinolones was evaluated by site-directed mutagenesis. Results: Three different phenotypes (similar resistance, higher resistance or lower resistance to quinolones) were obtained in the random mutagenesis assays when compared with wild-type phenotypes. Only one mutant increased quinolone resistance: QnrS1 containing D185Y substitution (4-fold for ciprofloxacin). Using site-directed mutagenesis, residues G56, C72, C92, G96, F114, C115, S116, A117 and L159, according to the sequence of QnrA1, were analysed and despite the wide amino acid variability of the PRPs, most conserved residues analysed were critical to QnrA1, QnrB1 and QnrS1. Conclusions: Amino acid sequences of PRPs QnrA1, QnrB1 and QnrS1 could be already optimized for quinolone resistance. One or several changes appear to be insufficient to obtain variants producing fluoroquinolone clinical resistance (MIC > 1 mg/L). Critical residues for quinolone resistance in PRPs were described. Interestingly, different effects were observed for QnrA1, QnrB1 and QnrS1 with the same substitution in several positions.