Type II topoisomerase mutations in clinical isolates of Enterobacter cloacae and other enterobacterial species harbouring the qnrA gene

Lascols, Christine; Robert, Jérôme; Cattoir, Vincent; Bebear, Cécile; Cavallo, Jean-Didier; Podglajen, Isabelle; Ploy, Marie-Cécile; Bonnet, Richard; Soussy, Claude-James; Cambau, Emmanuelle

doi:10.1016/j.ijantimicag.2006.11.008

Cited by 46 publications

(35 citation statements)

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“…This finding is consistent with other reports. A previously reported study indicated that 25 of 28 (89%) clinical strains of E. cloacae and other enterobacterial species that harbored qnrA had mutations in the GyrA gyrase subunit and ParC topoisomerase subunit (8). A ciprofloxacin-resistant (MIC Ͼ 32 g/ml) E. coli isolate, isolate 1B, was isolated from a urinary specimen of a Canadian patient treated with norfloxacin for infection due to a ciprofloxacin-susceptible isolate, isolate 1A.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Expression of the Plasmid-Mediated Quinolone Resistance Determinant qnrA1

Shi

et al. 2007

Antimicrob Agents Chemother

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Since its discovery, qnrA has been found in most common Enterobacteriaceae. Ciprofloxacin MICs conferred by different qnrA-positive plasmids could range from 0.1 g/ml to 2 g/ml in Escherichia coli J53. The reasons for different ciprofloxacin MICs conferred by qnrA have not been fully clarified. Five hundred forty-one consecutive gram-negative clinical strains that were resistant or intermediate to ciprofloxacin and that were isolated in Shanghai in 2005 were screened for qnrA by PCR. For qnrA-positive isolates, the transferability of quinolone resistance was determined by conjugation and mutations within the quinolone resistance-determining region (QRDR) of gyrA and parC. aac(6)-Ib-cr was detected and qnrA RNA expression was determined using real-time reverse transcription-PCR for transconjugants with different ciprofloxacin MICs. The qnrA gene was detected in 7 of the 541 clinical isolates. Quinolone resistance was transferred in four strains by conjugation. Mutations in the QRDR of gyrA and parC were detected in five qnrA-positive clinical strains with higher ciprofloxacin MICs. Of four qnrA-bearing plasmids in E. coli J53, pHS4 and pHS5 conferred ciprofloxacin MICs of 0.094 to 0.125 g/ml; pHS3, which harbored the aac(6)-Ib-cr gene as well, conferred a ciprofloxacin MIC of 0.25 g/ml, and pHS6, which had both the aac(6)-Ib-cr gene and a high expression level of qnrA, had a ciprofloxacin MIC of 1.0 g/ml. The prevalence of qnrA appeared to be higher in Enterobacter cloacae than in other Enterobacteriaceae. The coexistence of qnrA and aac(6)-Ib-cr in a single plasmid and increased qnrA expression can account for the different levels of ciprofloxacin resistance seen in transconjugants.Plasmid-mediated quinolone resistance associated with the qnrA gene was discovered in 1998 (10). The originally described qnr gene is now referred to as qnrA because of recent findings of other related qnr genes, qnrB (7) and qnrS (5). Since the discovery of qnrA, qnrA was found in almost all populated continents and in most common Enterobacteriaceae including Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter freundii, and Providencia stuartii (6, 16). The prevalence of qnrA varied from less than 1% to higher than 20%, depending on the population sampled. Plasmids harboring qnrA may also encode an extended-spectrum ␤-lactamase (ESBL) (6). qnrA was absent in nonfermenting gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter spp. in small surveys, but whether the lack of detection reflects a true absence or the small number of strains tested is not clear (16). Most of these studies screened for qnrA from clinical isolates collected in the late 1990s or early 2000s, several years prior to each study. Usually, the strains screened had additional restriction conditions such as resistance to expandedspectrum cephalosporins or carriage of genes encoding ESBLs simultaneously. Consecutive strains of Enterobacteriaceae were screened for qnrA in a few surveys (1).qnrA conferred a low level of quinolone resistan...

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Section: Discussionmentioning

confidence: 99%

Prevalence and Expression of the Plasmid-Mediated Quinolone Resistance Determinant qnrA1

Shi

et al. 2007

Antimicrob Agents Chemother

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“…This occurrence has been usually but not exclusively qnrS with either qnrB or qnrA (27,85,110,217). Whether multiple Qnr proteins have an additive effect on the MIC is unclear.…”

Section: Resistance Activity Of a Combination Of Qnr Proteinsmentioning

confidence: 99%

Plasmid-Mediated Quinolone Resistance: a Multifaceted Threat

et al. 2009

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SUMMARY Although plasmid-mediated 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. The best-described form of PMQR is determined by the qnr group of genes. These genes, likely originating in aquatic organisms, code for pentapeptide repeat proteins. These proteins reduce susceptibility to quinolones by protecting the complex of DNA and DNA gyrase or topoisomerase IV enzymes from the inhibitory effect of quinolones. Two additional PMQR mechanisms were recently described. aac(6′)-Ib-cr encodes a variant aminoglycoside acetyltransferase with two amino acid alterations allowing it to inactivate ciprofloxacin through the acetylation of its piperazinyl substituent. oqxAB and qepA encode efflux pumps that extrude quinolones. All of these genes determine relatively small increases in the MICs of quinolones, but these changes are sufficient to facilitate the selection of mutants with higher levels of resistance. The contribution of these genes to the emergence of quinolone resistance is being actively investigated. Several factors suggest their importance in this process, including their increasing ubiquity, their association with other resistance elements, and their emergence simultaneous with the expansion of clinical quinolone resistance. Of concern, these genes are not yet being taken into account in resistance screening by clinical microbiology laboratories.

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“…The same augmentation of resistance selection has been found in clinical isolates of E. cloacae (147). Surprisingly, in qnr-harboring E. coli gyrA resistance mutants are rarely selected (217), although resistance produced by qnr and gyrA is additive (218)(219)(220), clinical isolates with qnr alleles or aac(6′)-Ib-cr and gyrA, parC, and other resistance mutations are common (221), and gyrA mutants have developed in qnr positive isolates from patients treated with quinolone for E. coli (222) or S. enterica (223) infections.…”

Section: Resistance Produced By Pmqr Determinantsmentioning

confidence: 99%

Plasmid-Mediated Quinolone Resistance

Jacoby

2009

Antimicrobial Drug Resistance

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SummaryThree 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.

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Type II topoisomerase mutations in clinical isolates of Enterobacter cloacae and other enterobacterial species harbouring the qnrA gene

Cited by 46 publications

References 49 publications

Prevalence and Expression of the Plasmid-Mediated Quinolone Resistance Determinant qnrA1

Prevalence and Expression of the Plasmid-Mediated Quinolone Resistance Determinant qnrA1

Plasmid-Mediated Quinolone Resistance: a Multifaceted Threat

Plasmid-Mediated Quinolone Resistance

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