Mobilization of qnrB2 and ISCR1 in plasmids

Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli, Taiwan.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 03/2009; 53(3):1235-7. DOI: 10.1128/AAC.00970-08
Source: PubMed


The DNA sequences of two IncHI2 plasmids, pEC-IMP and pEC-IMPQ, from metallo-β-lactamase-producing Enterobacter cloacae clinical isolates were determined. The two conjugative plasmids are almost identical, but pEC-IMPQ carries an additional
segment containing an orf513 (ISCR1), a truncated 3′ conserved sequence, and a qnrB2. Comparative analyses provide support for the proposed ISCR1-mediated gene mobilization.

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Available from: Ying-Tsong Chen, Feb 17, 2014
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    • "Since then, ISCR1 elements were shown to have a close association with trimethoprim, quinolone, aminoglycoside resistance genes and several β-lactamase genes. Two copies of ISCR1 with a 3′CS upstream flanking different subtypes of qnr genes were also reported in China [27], France [17] and other countries [28]. blaNDM-1 has always been found to be carried on a structure consisting of a partial ISAba125 and a bleMBL gene with blaNDM-1 sandwiched between them [3]. "
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    ABSTRACT: The gene for New Delhi metallo-β-lactamase 1 (NDM-1) has been reported to be transmitted via plasmids which are easily transferable and capable of wide distribution. We report the isolation of two NDM-1 producing strains and possible in vivo transfer of blaNDM-1 in a patient. Clinical samples were collected for bacterial culture and antibiotic susceptibility testing from a patient during a 34-day hospitalization. The presence of blaNDM-1 was detected by PCR and sequencing. Plasmids of interest were sequenced. Medical records were reviewed for evidence of association between the administration of antibiotics and the acquisition of the NDM-1 resistance. A NDM-1 positive Raoultella planticola was isolated from blood on the ninth day of hospitalization without administration of any carbapenem antibiotics and a NDM-1 positive Escherichia coli was isolated from feces on the 29th day of hospitalization and eight days after imipenem administration. The blaNDM-1 was carried by a 280 kb plasmid pRpNDM1-1 in R. planticola and a 58 kb plasmid pEcNDM1-4 in E. coli. The two plasmids shared a 4812 bp NDM-1-ISCR1 element which was found to be excisable from the plasmid as a free form and transferrable in vitro to a NDM-1 negative plasmid from E. coli. blaNDM-1 was embedded in an ISCR1 complex class 1 integron as a novel 4812 bp NDM-1-ISCR1 element. The element was found to be able to self excise to become a free form, which may provide a new vehicle for NDM-1 dissemination. This mechanism could greatly accelerate the spread of NDM-1 mediated broad spectrum β-lactam resistance.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "Also, the resistance to gentamicin and tobramycin was cotransferred. It is recognized that insertion sequences (IS), as ISCR1 or ISEcp1 associated with qnrB genes, provide a putative promoter region for the expression of genes encoding resistance to aminoglycosides, trimethoprim, chloramphenicol, and β-lactams [6, 21]. Additionally, the coexistence between qnr and aminoglycosides was expected because qnrB genes are frequently located in integrons [6, 9]. "
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    ABSTRACT: Four nontyphoidal Salmonella strains with resistance to extended-spectrum cephalosporins and nonclassical quinolone resistance phenotype were studied. Two S. Give were isolated from pediatric patients with acute gastroenteritis, and two S. Heidelberg were recovered from raw chicken meat. Phenotypic characterization included antimicrobial susceptibility testing and detection of extended-spectrum β -lactamases (ESBLs) by the double-disc synergy method. The detection of quinolone resistance-determining regions (QRDR) of gyrA, gyrB, and gyrC genes, bla ESBLs genes, and plasmid-mediated quinolone resistance (PMQR) determinants was carried out by molecular methods. Plasmid analysis included Southern blot and restriction patterns. Transferability of resistance genes was examined by transformation. bla TEM-1 + bla SHV-12 genes were detected in S. Give SG9611 and bla TEM-1 + bla CTX-M-2 in the other three strains: S. Give SG9811, S. Heidelberg SH7511, and SH7911. Regardless of origin and serovars, the qnrB19 gene was detected in the 4 strains studied. All determinants of resistance were localized in plasmids and successfully transferred by transformation. This study highlights the circulation of qnrB19 associated with bla TEM-1, bla SHV-12, and bla CTX-M-2 in S. Give and S. Heidelberg in Venezuela. The recognition of factors associated with increasing resistance and the study of the molecular mechanisms involved can lead to a more focused use of antimicrobial agents.
    Full-text · Article · Sep 2013 · International Journal of Microbiology
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    • "Currently, there are four main plasmid-mediated quinolone resistance (PMQR) mechanisms: the determinant Qnr, which includes genes such as qnrA, qnrB, qnrS, with several variants each, and qnrC and qnrD, that increase resistance to both nalidixic acid and fluoroquinolones (Tran and Jacoby, 2002; Hata et al., 2005; Jacoby et al., 2006; Wang et al., 2009; Cavaco et al., 2009); the cr variant of the common aminoglycoside acetyltransferase Aac(6 0 )-Ib, which is capable of acetylate and reduce the activity of certain fluoroquinolones (Robicsek et al., 2006); the QepA determinant, an efflux pump that confers decreased susceptibility to hydrophilic fluoroquinolones; and the multi-resistance (MR) efflux pump OqxAB that is also able to confer resistance to nalidixic acid and ciprofloxacin, among other antimicrobial agents (Poirel et al., 2012). These PMQR mechanisms are frequently associated to transference events, which can be facilitated by their location on mobile genetic elements, such as transposons, insertion sequences, and integrons gene cassettes, among others, leading to the establishment of MR (Chen et al., 2009; García-Ferná ndez et al., 2009). "
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    ABSTRACT: Enterobacteriaceae resistant to quinolones frequently arise in animals, being easily disseminated through the food-chain. The aim of this study was to investigate the presence of plasmid-mediated quinolone resistance (PMQR) determinants in Salmonella spp. (n=183) and Escherichia coli (n=180) isolates, collected from food-producing animals and food products among swine, poultry, rabbits and cattle. All isolates were subjected to antimicrobial susceptibility testing and molecular screening of PMQR determinants. β-Lactamase-encoding genes, and the quinolone resistance determining region (QRDR) of gyrA, gyrB, parC and parE genes were also investigated in PMQR-positive isolates. Plasmid characterization was performed by conjugation, followed by replicon-typing. Genetic relatedness of PMQR-positive E. coli was examined by Multilocus Sequence Typing, while Salmonella was previously serotyped. The association of mobile genetic elements and PMQR was investigated through PCR mapping assays. Overall, 4.1% (15/363) isolates harbored qnrB2 (n=3), qnrB19 (n=3), and qnrS1 (n=9) genes. All but one isolate presented one to four mutations in QRDR of gyrA or parC genes, which is consistent with the range of MIC values detected (0.19-64mg/L) for ciprofloxacin; 60% (9/15) of qnr-harboring isolates were non-susceptible to β-lactam antibiotics which was justified by the presence of β-lactamases from TEM (TEM-1, n=8; TEM-135, n=1) and SHV (SHV-108, n=1) families. Analysis of mobile genetic elements revealed that qnr genes were detected nearby relevant genetic elements like intI1, ISEcl2, IS26 and ISCR1 and enclosed in diverse Inc. type plasmids. This study illustrated the existence of Qnr-producing E. coli and Salmonella from food-producing animals, associated to specific mobile elements that might mediate their transference between species and among distinct settings.
    Full-text · Article · Aug 2013 · Veterinary Microbiology
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