Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Escherichia coli

Kern, Winfried V.; Steinke, Petra; Schumacher, Anja; Schuster, Sabine; Baum, Heike von; Bohnert, Jürgen A.

doi:10.1093/jac/dki445

Cited by 140 publications

(111 citation statements)

References 15 publications

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“…CLSI breakpoints were used when available and antimicrobial breakpoints that were not included in the CLSI were defined by a population of the isolates that were tested in this study. The concentrations of PAβN (80 µg/ml) and NMP (160 µg/ml) were based on their available ranges, as previously described [14,31].…”

Section: Methodsmentioning

confidence: 99%

Contribution of the AcrAB-TolC Efflux Pump to High-Level Fluoroquinolone Resistance in <i>Escherichia coli</i> Isolated from Dogs and Humans

Sato

Yokota

Okubo

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. Fluoroquinolone resistance is mainly caused by mutations in quinolone resistance-determining regions of DNA gyrase and topoisomerase IV in Escherichia coli. The AcrAB-TolC efflux pump contributes to resistance against fluoroquinolone and other antimicrobials. In this study, we investigated a high-level mechanism of fluoroquinolone resistance in E. coli that was isolated from human clinical samples and canine fecal samples. E. coli strains with high levels of fluoroquinolone resistance have been found to be frequently resistant to cephalosporins. Strains with high-level fluoroquinolone resistance exhibited lower intracellular enrofloxacin (ENR) concentrations, higher expression of AcrA, and a greater reduction in the fluoroquinolone minimum inhibitory concentration for treatment with an efflux pump inhibitor. The frequency of strains with enhanced ENR resistance selection and the survival rate of E. coli in the presence of ENR in vitro were correlated well with AcrA protein expression levels in the parental strains. These results suggest that AcrAB-TolC efflux pump over-expression is related to high-level fluoroquinolone resistance and the selection of strains with enhanced fluoroquinolone resistance. Antimicrobials that are intended for human use are also used on companion animals. Their excessive and inappropriate administration in animals leads to the generation and spread of antimicrobial-resistant bacteria, which in veterinary medicine represent a potential hazard to human health [1,26,33,36]. Companion animals live in close proximity to humans and receive medical treatment more frequently than food-producing animals [23]. Platell et al. reported that some fluoroquinolone-resistant Escherichia coli isolates that were derived from companion animals (i.e., dogs and cats) were very similar to the ones found in humans [27].Fluoroquinolones are widely used to treat various bacterial infections in humans and companion animals. E. coli infections, especially urinary tract infections, are frequently treated with fluoroquinolones. Thus, fluoroquinolone resistance has increased among clinical isolates of humans and companion animals [7,24]. Previous studies reported that extended-spectrum β-lactamase (ESBL)-producing E. coli and Klebsiella pneumoniae are frequently resistant to fluoroquinolone [20,30,32]. Cephalosporins and fluoroquinolones are among the most important antimicrobials that are used on humans and animals, mainly because of their broad-spectrum effectiveness against both gram-positive and gram-negative bacteria. Therefore, the appearance of fluoroquinolone-and/ or cephalosporin-resistant bacteria is a serious problem in clinical medicine.Fluoroquinolone resistance mechanisms are mainly based on chromosomal mutations in the quinolone resistancedetermining regions (QRDRs) of gyrA and gyrB, which encode DNA gyrase subunits, and parC and pare, which encode topoisomerase IV subunits [2,8,11,37]. Resistance to nalidixic acid (NAL) and slightly decreased susceptibility to fluoroquinolones is attribute...

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Section: Methodsmentioning

confidence: 99%

Contribution of the AcrAB-TolC Efflux Pump to High-Level Fluoroquinolone Resistance in <i>Escherichia coli</i> Isolated from Dogs and Humans

Sato

Yokota

Okubo

et al. 2013

The Journal of Veterinary Medical Science

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“…Several studies have used 100 mg NMP ml -1 in E. coli (Bohnert & Kern, 2005;Kern et al, 2006;Schumacher et al, 2006), Acinetobacter baumannii (Pannek et al, 2006) and Campylobacter species (Hannula & Hänninen, 2008) to obtain better inhibition in RND-type overexpressing efflux pump systems.…”

Section: Discussionmentioning

confidence: 99%

“…Efflux pump inhibitors (EPIs) are drugs able to modify resistance by blocking bacterial pumps. Several arylpiperidines and other compounds capable of reversing MDR in E. coli and other members of the Enterobacteriaceae have been studied extensively (Bean & Wareham, 2009;Bohnert & Kern, 2005;Coban et al, 2009;Kern et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Effect of 1-(1-naphthylmethyl)-piperazine on antimicrobial agent susceptibility in multidrug-resistant isogenic and veterinary Escherichia coli field strains

Marchetti

Errecalde

Mestorino

2012

Journal of Medical Microbiology

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The objective of this study was to evaluate the interaction of the efflux pump inhibitor 1-(1-naphthylmethyl)-piperazine (NMP) when combined with different families of antimicrobial agents against isogenic strains and multidrug-resistant (MDR) Escherichia coli field strains isolated from animals. Laboratory isogenic strains of E. coli with different levels of expression of efflux pumps were used as quality controls. Ten MDR E. coli strains were collected from healthy animals in a cross-sectional study in four commercial dairy farms. The MICs of florfenicol, ciprofloxacin, tetracycline and ampicillin were determined by a serial microdilution method in Luria-Bertani broth in the presence or absence of NMP. NMP used with ampicillin exerted no effect on the isogenic or field strains. In most of the field MDR E. coli strains and in an acrAB-overexpressing (AG112) isogenic strain, the MICs of florfenicol, ciprofloxacin and tetracycline decreased at least fourfold when the antimicrobial was combined with the highest NMP concentrations. In the wild-type strain (AG100), there were no decreases of more than twice the MIC, whilst in strain AG100A, an efflux pump-deficient strain, the MIC did not change, regardless of the concentration of NMP used with these three antimicrobials. Thus, ampicillin was not affected by the efflux pump mechanism, whereas ciprofloxacin, tetracycline and florfenicol were shown to be substrates of efflux pumps, with a consequent significant reduction in MICs. Resistance could not be completely reversed in the E. coli field strains by NMP, probably because other resistance mechanisms were also present. However, in strain AG112, the MIC results demonstrated that NMP expressed an important synergistic activity with florfenicol. The reduction in florfenicol MIC value was sufficient to reverse antimicrobial resistance completely for AG112.

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“…Para a determinação da concentração inibitória mínima (CIM) e do sistema de efluxo multidrogas, foi seguida a metodologia de Moreira et al (2005) Kern et al (2006). Empregaram-se 50µg/mL de PAβN e 75µg/mL de NMP.…”

Section: Methodsunclassified

Sistemas de efluxo multidrogas em Escherichia coli e uso de inibidores como possíveis adjuvantes na terapia da mastite bovina

Ospina

Pieri

Pietralonga

et al. 2014

Arq. Bras. Med. Vet. Zootec.

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Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Escherichia coli

Abstract: NMP is moderately active in reversing MDR in clinical isolates of E. coli and can partially restore fluoroquinolone susceptibility through inhibition of efflux pumps.

Cited by 140 publications

References 15 publications

Contribution of the AcrAB-TolC Efflux Pump to High-Level Fluoroquinolone Resistance in <i>Escherichia coli</i> Isolated from Dogs and Humans

Contribution of the AcrAB-TolC Efflux Pump to High-Level Fluoroquinolone Resistance in <i>Escherichia coli</i> Isolated from Dogs and Humans

Effect of 1-(1-naphthylmethyl)-piperazine on antimicrobial agent susceptibility in multidrug-resistant isogenic and veterinary Escherichia coli field strains

Sistemas de efluxo multidrogas em Escherichia coli e uso de inibidores como possíveis adjuvantes na terapia da mastite bovina

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