Impact of plasmid-borne oqxAB on the development of fluoroquinolone resistance and bacterial fitness in Escherichia coli

Wang, Jing; Guo, Zewen; Zhi, Chanping; Yang, Tong; Zhao, Jingjing; Chen, Xiaojie; Zeng, Li; Lv, Luchao; Zeng, Zhenling; Liu, Jianhua

doi:10.1093/jac/dkw576

Cited by 21 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to chromosomally-encoded efflux pumps, the presence of plasmid-encoded efflux pump genes oqxAB and qepA has been shown to increase ciprofloxacin MIC in E. coli . 34,35 oqxAB confers a median fold increase in MIC of 7.5 (range 2-16x fold increase) 35, 62–64 , while qepA confers a median fold increase of 4.5 (range 2-31x fold increase, Table 2). 34,52,65–68…”

Section: Resultsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

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

View full text Add to dashboard Cite

show abstract

“…This is the first report of the coexistence of three PMQR genes on a multiple resistance plasmid. 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: 98%

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

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.

show abstract

“…The stability of the mcr-1 –positive plasmids was investigated in vitro according to a previously described protocol (Bryksin and Matsumura, 2010 ; Wang et al, 2017 ). In brief, transconjugants E. coli DH5α/pHNSHP45, E. coli DH5α/pHNSHP45-2, E. coli DH5α/pHNSHP23, E. coli DH5α/pHNSHP17, and E. coli DH5α/ pHNSHP24 were propagated by serial transfer for 14 days of passage.…”

Section: Methodsmentioning

confidence: 99%

Fitness Advantage of mcr-1–Bearing IncI2 and IncX4 Plasmids in Vitro

et al. 2018

Front. Microbiol.

Self Cite

105

101

View full text Add to dashboard Cite

The objective of this study was to assess the impact of diverse plasmids bearing colistin resistance gene mcr-1 on host fitness. Forty-seven commensal E. coli isolates recovered from the pig farm where mcr-1 was first identified were screened for mcr-1. mcr-1-bearing plasmids were characterized by sequencing. The fitness impact of mcr-1-bearing plasmids was evaluated by in vitro competition assays. Twenty-seven (57.5%) E. coli isolates were positive for mcr-1. The mcr-1 genes were mainly located on plasmids belonging to IncI2 (n = 5), IncX4 (n = 11), IncHI2/ST3 (n = 8), IncFII (n = 2), and IncY (n = 2). InHI2 plasmids also carried other resistance genes (floR, blaCTX−M, and fosA3) and were only detected in isolates from nursery pigs. Sequences of the representative mcr-1–bearing plasmids were almost identical to those of the corresponding plasmid types reported previously. An increase in the fitness of IncI2- and IncX4-carrying strains was observed, while the presence of IncHI2, IncFII and IncY plasmids showed a fitness cost although an insignificant fitness increase was initially observed in IncFII or IncY plasmids-containing strains. Acquisition of IncI2-type plasmid was more beneficial for host E. coli DH5α than either IncHI2 or IncX4 plasmid, while transformants with IncHI2-type plasmid presented a competitive disadvantage against IncI2 or IncX4 plasmid containing strains. In conclusion, IncI2, IncX4, and IncHI2 were the major plasmid types driving the dissemination of mcr-1 in this farm. Increased fitness or co-selection by other antimicrobials might contribute to the further dissemination of the three epidemic mcr-1–positive plasmids (IncI2, IncX4, and IncHI2) in this farm and worldwide.

show abstract

Impact of plasmid-borne oqxAB on the development of fluoroquinolone resistance and bacterial fitness in Escherichia coli

Abstract: The possession of plasmid-borne oqxAB may facilitate the evolution of fluoroquinolone resistance, and the fitness cost of OqxAB-encoding plasmids could be compensated by additional chromosomal mutations.

Cited by 21 publications

References 30 publications

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

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

Fitness Advantage of mcr-1–Bearing IncI2 and IncX4 Plasmids in Vitro

Contact Info

Product

Resources

About