Impact of AAC(6′)-Ib-cr in combination with chromosomal-mediated mechanisms on clinical quinolone resistance in<i>Escherichia coli</i>

Machuca, Jesús; Ortíz, Manuel; Recacha, Esther; Díaz-de-Alba, Paula; Docobo-Pérez, Fernando; Rodríguez-Martínez, José Manuel; Pascual, Álvaro

doi:10.1093/jac/dkw258

Cited by 46 publications

(27 citation statements)

References 17 publications

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“…Studies showed that PMQR was usually low level, and its MIC value was below the CLSI resistance breakpoint [21]. The MIC of c749 demonstrated intermediate resistance, which indicated that the coexistence of three PMQR genes can cause an increase in MIC more than the presence of one or two PMQR genes reported [22,23].…”

Section: Discussionmentioning

confidence: 99%

Emerging coexistence of three PMQR genes on a multiple resistance plasmid with a new surrounding genetic structure of qnrS2 in E. coli in China

Ying

Zhou

Xie

et al. 2020

Antimicrob Resist Infect Control

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Background: Quinolones are commonly used for treatment of infections by bacteria of the Enterobacteriaceae family. However, the rising resistance to quinolones worldwide poses a major clinical and public health risk. This study aimed to characterise a novel multiple resistance plasmid carrying three plasmid-mediated quinolone resistance genes in Escherichia coli clinical stain RJ749. Methods: MICs of ceftriaxone, cefepime, ceftazidime, ciprofloxacin, and levofloxacin for RJ749 and transconjugant c749 were determined by the Etest method. Conjugation was performed using sodium azide-resistant E. coli J53 strain as a recipient. The quinolone resistance-determining regions of gyrA, gyrB, parC, and parE were PCR-amplified. Results: RJ749 was highly resistant to quinolones, while c749 showed low-level resistance. S1-nuclease pulsed-field gel electrophoresis revealed that RJ749 and c749 both harboured a plasmid. PCR presented chromosomal mutation sites of the quinolone resistance-determining region, which mediated quinolone resistance. The c749 genome comprised a single plasmid, pRJ749, with a multiple resistance region, including three plasmid-mediated quinolone resistance (PMQR) genes (aac (6′)-Ib-cr, qnrS2, and oqxAB) and ten acquired resistance genes. One of the genes, qnrS2, was shown for the first time to be flanked by two IS26s. Three IS26-mediated circular molecules carrying the PMQR genes were detected. Conclusions:We revealed the coexistence of three PMQR genes on a multiple resistance plasmid and a new surrounding genetic structure of qnrS2 flanked by IS26 elements. IS26 plays an important role in horizontal spread of quinolone resistance.

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Section: Discussionmentioning

confidence: 99%

Emerging coexistence of three PMQR genes on a multiple resistance plasmid with a new surrounding genetic structure of qnrS2 in E. coli in China

Ying

Zhou

Xie

et al. 2020

Antimicrob Resist Infect Control

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“…A similar positive epistatic effect was observed for chromosomal gyrA / parC mutations together with plasmid-mediated resistance determinants qepA 67 and aac(6’)Ib-cr . 52,75 However, experimental studies of combinations of gyrA and parC mutations with qnr genes showed discordant results. One study reported a negative epistatic effect on ciprofloxacin MIC of target alteration mutations with all qnr genes tested ( qnrA , qnrB , qnrC , qnrD , qnrS ) 59 , and another study observed a similar effect of target alteration mutations with qnrB , but the opposite effect for target alteration mutations with qnrS in terms of conferred MIC.…”

Section: Discussionmentioning

confidence: 99%

Quantifying the contribution of four resistance mechanisms to ciprofloxacin minimum inhibitory concentration inEscherichia coli: a systematic review

Remondini

Pasquini

et al. 2018

Preprint

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SynopsisIntroductionCiprofloxacin resistance in Escherichia coli is widespread and adds to the burden of E. coli infections. Reviews assessing the genetic basis of ciprofloxacin resistance have mostly been qualitative. However, to allow for the prediction of a resistance phenotype of clinical relevance based on genotypic characteristics, it is essential to quantify the contribution of prevalent genotypic determinants to resistance. We carried out a systematic review to assess the relative contribution of currently known genomic resistance determinants to the minimum inhibitory concentration (MIC) of ciprofloxacin in E. coli.MethodsPubMed and Web of Science were searched for English language studies that assessed both ciprofloxacin MIC and the presence or introduction of genetic determinants of ciprofloxacin resistance in E. coli. We included experimental and observational studies without time restrictions. Medians and ranges of MIC fold changes were calculated for each resistance determinant and for combinations of determinants.ResultsWe included 66 studies, describing 604 E. coli isolates that carried at least one genetic resistance determinant. Genes coding for targets of ciprofloxacin (gyrA and parC) are strongest contributors to ciprofloxacin resistance, with median MIC fold increases ranging from 24 (range 4-133) for single Ser83Leu (gyrA) mutants to 1533 (range 256-8533) for triple Ser83Leu, Asp87Asn/Gly (gyrA) and Ser80Ile/Arg (parC) mutants. Other resistance mechanisms, including efflux, physical blocking or enzymatic modification, conferred smaller increases in ciprofloxacin MIC (median MIC fold increases typically around 15, range 1-125). However, the (combined) presence of these other resistance mechanisms further increases resistance with median MIC fold increases of up to 4000, and even in the absence of gyrA and parC mutations up to 250.ConclusionThis report provides a comprehensive and quantitative overview of the contribution of different genomic determinants to ciprofloxacin resistance in E. coli. Additionally, the data demonstrate the complexity of resistance phenotype prediction from genomic data and could serve as a reference point for studies aiming to address ciprofloxacin resistance prediction using genomics, in E. coli.

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“…Studies showed that PMQR was usually low level, and its MIC value was below the CLSI resistance breakpoint [20]. The MIC of c749 demonstrated intermediate resistance, which indicated that the coexistence of three PMQR genes can cause an increase in MIC more than the presence of one or two PMQR genes reported [21,22].…”

Section: Discussionmentioning

confidence: 99%

Emerging coexistence of three PMQR genes on a multiple resistance plasmid with a new surrounding genetic structure of qnrS2 in E. coli in China

Ying

Zhou

Xie

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Quinolones are commonly used for treatment of infections by bacteria of the Enterobacteriaceae family. However, the rising resistance to quinolones worldwide poses a major clinical and public health risk. This study aimed to characterise a novel multiple resistance plasmid carrying three plasmid-mediated quinolone resistance genes in Escherichia coli clinical stain RJ749. Methods: MICs of ceftriaxone, cefepime, ceftazidime, ciprofloxacin, and levofloxacin for RJ749 and transconjugant c749 were determined by the Etest method. Conjugation was performed using sodium azide-resistant E. coli J53 strain as a recipient. The quinolone resistance-determining regions of gyrA, gyrB, parC, and parE were PCR-amplified. Results: RJ749 was highly resistant to quinolones, while c749 showed low-level resistance. S1-nuclease pulsed-field gel electrophoresis revealed that RJ749 and c749 both harboured a plasmid. PCR presented chromosomal mutation sites of the quinolone resistance-determining region, which mediated quinolone resistance. The c749 genome comprised a single plasmid, pRJ749, with a multiple resistance region, including three plasmid-mediated quinolone resistance (PMQR) genes (aac(6′)-Ib-cr, qnrS2, and oqxAB) and ten acquired resistance genes. One of the genes, qnrS2, was shown for the first time to be flanked by two IS26s. Three IS26-mediated circular molecules carrying the PMQR genes were detected. Conclusions: We revealed the coexistence of three PMQR genes on a multiple resistance plasmid and a new surrounding genetic structure of qnrS2 flanked by IS26 elements. IS26 plays an important role in horizontal spread of quinolone resistance.

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Impact of AAC(6′)-Ib-cr in combination with chromosomal-mediated mechanisms on clinical quinolone resistance inEscherichia coli

Abstract: The aac(6')-Ib-cr gene, in spite of producing low-level resistance by itself, plays a relevant role in acquisition of a clinical level of ciprofloxacin and norfloxacin resistance, when combined with three or four chromosomal mutations, both in vitro and in vivo.

Cited by 46 publications

References 17 publications

Emerging coexistence of three PMQR genes on a multiple resistance plasmid with a new surrounding genetic structure of qnrS2 in E. coli in China

Emerging coexistence of three PMQR genes on a multiple resistance plasmid with a new surrounding genetic structure of qnrS2 in E. coli in China

Quantifying the contribution of four resistance mechanisms to ciprofloxacin minimum inhibitory concentration inEscherichia coli: a systematic review

Emerging coexistence of three PMQR genes on a multiple resistance plasmid with a new surrounding genetic structure of qnrS2 in E. coli in China

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