Selected Arylpiperazines Are Capable of Reversing Multidrug Resistance in
            <i>Escherichia coli</i>
            Overexpressing RND Efflux Pumps

Bohnert, Jiirgen A.; Kern, Winfried V.

doi:10.1128/aac.49.2.849-852.2005

Cited by 194 publications

(156 citation statements)

References 9 publications

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“…5). A number of efflux pump inhibitors phenylalanine-arginine β-naphthylamide (PAβN) [26][27], 1-1-Naphthylmethyl-piperazine (NMP), pyridopyrimidine one and pyrazolopyridines) exerted their inhibitory activity against bacterial efflux pump at concentration range from 70 µg/ml [28] to 100 µg/ml [29], for example, PAβN registered half maximum activity approximately at 70 µg/ml whereas NMP caused EtBr accumulation at 100 µg/ml. An EPI (such as NMP) can also act as antibacterial agent at four-fold (400 µg/ml) concentration to its normal EPI concentration.…”

Section: Typhi Over-expressing Efflux Pumps As Indicated By Etbr Carmentioning

confidence: 99%

Anticancer Drugs as Prospective Efflux Pump Inhibitors for Salmonella Typhi Produce Conflicting Results in in Silico and in Vitro Studies

Gupta

Gautam

Rai

2016

Int J Pharm Pharm Sci

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Objective: Anticancer drugs paclitaxel and vinblastine were tested for their potential as efflux pump inhibitors for Salmonella Typhi-based on in silico and in vitro studies.Methods: Three-dimensional protein models of AcrAB-TolC of Salmonella Typhi were generated by online server PHYRE-2. The quality of 3D structures was assessed by PROCHECK, SWISS MODEL. Docking analysis of anticancer drugs with AcrA, AcrB and TolC subunits were performed after refining the homology models with Modrefiner. Salmonella Typhi (S. Typhi) efflux pump activity was measured by ethidium bromide (EtBr) cartwheel and semi-automated fluorometry methods respectively. Fluorescence intensity in bacterial colonies was measured under different treatment conditions (with or without drugs) on Muller Hinton agar (MHA) plates containing EtBr in cartwheel assay. EtBr efflux assay was determined following the loading of bacteria with EtBr and fluorescence was recorded over fixed time period with the help of fluorescent spectrophotometer. The results obtained were compared with the control.Results: Efflux pump inhibitor (EPIs) activity of paclitaxel and vinblastine determined by EtBr cartwheel assay registered no activity whereas semiautomated fluorescent assay revealed marginal activity when compared to control. Conclusion:We report the conflicting result of in silico and in vitro studies in predicting the antimicrobial effect of mainstream anticancer drugs as efflux pump inhibitors for Salmonella Typhi.

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Section: Typhi Over-expressing Efflux Pumps As Indicated By Etbr Carmentioning

confidence: 99%

Anticancer Drugs as Prospective Efflux Pump Inhibitors for Salmonella Typhi Produce Conflicting Results in in Silico and in Vitro Studies

Gupta

Gautam

Rai

2016

Int J Pharm Pharm Sci

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“…Few compounds were identified as EPIs for AcrAB-TolC, for example: Arylpiperazines were suggested as MDR reversal agent for RND efflux pumps [10], quinolone derivatives were promising EPIs for AcrAB-TolC in Enterobacter aerogenes [11], artesunate enhances the activity of β-lactam antibiotics through inhibition of AcrAB-TolC of E. coli [12], pimozide inhibits the AcrAB-TolC of E. coli [13], and benzothiazoles were identified as potential AcrAB-TolC efflux pump inhibitors (EPIs) in E. coli [14].…”

Section: Introductionmentioning

confidence: 99%

Detection of potential AcrAB-TolC multidrug efflux pump inhibitor in calyces extract of Hibiscus sabdariffa

Al‐Karablieh¹,

Abu-Qatouseh²,

Aburjai³

2017

J Intercult Ethnopharmacol

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Aim: The aim of this study is to investigate the occurrence of potential efflux pump inhibitor (EPI) against AcrAB-TolC efflux pump in the methanol extract of Hibiscus sabdariffa. Materials and Methods: Calyces of H. sabdariffa were purchased from the local market in April 2014, used in methanol extraction. The methanol extract of H. sabdariffa was subjected to agar plate diffusion against Escherichia coli TG1 and its ∆acrB-∆tolC followed by a thin layer chromatography (TLC) bioassay. The fraction corresponding to EPI fraction was eluted from the silica gel by methanol. The synergistic effect of antimicrobials and EPI fraction was measured by minimum inhibitory concentration (MIC) determination for E. coli and Erwinia amylovora strains. The ability of EPI fraction to enhance ethidium bromide (EtBr) accumulation was conducted. Results: E. coli TG1 was more sensitive to the methanol extracts of H. sabdariffa than E. coli ∆acrB-∆tolC. Inhibition zone corresponding to flavones on TLC bioassay plate has been formed which might be related to the fraction of potential EPI. The MIC values revealed that EPI fraction enhanced the activity of the used antimicrobials by 4-8 folds in E. coli TG1 and by 4-10 folds in E. amylovora 1189. Addition of EPI fraction in a dose-dependent manner increased the intercellular accumulation of EtBr in the wild type stains of E. coli TG1 and E. amylovora 1189. Conclusion: An EPI fraction behaves like a multidrug EPI, and further investigation should be conducted for determination the structure of chemical constituents in EPI fraction.

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“…It has been shown that PAbN is able to reverse antimicrobial resistance in some selected MDR Gram-negative bacteria. However, PAbN showed intrinsic antibacterial activity against E. coli strains without expression of AcrAB efflux pumps, and exerted its effect through additional mechanisms unrelated to pump inhibition (Bohnert & Kern, 2005;Pannek et al, 2006;Sáenz et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Phe-Arg-b-naphthylamide (PAbN) is an EPI that has been studied by a number of authors (Bohnert & Kern, 2005;Pannek et al, 2006;Sáenz et al, 2004). It has been shown that PAbN is able to reverse antimicrobial resistance in some selected MDR Gram-negative bacteria.…”

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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Selected Arylpiperazines Are Capable of Reversing Multidrug Resistance in Escherichia coli Overexpressing RND Efflux Pumps

Cited by 194 publications

References 9 publications

Anticancer Drugs as Prospective Efflux Pump Inhibitors for Salmonella Typhi Produce Conflicting Results in in Silico and in Vitro Studies

Anticancer Drugs as Prospective Efflux Pump Inhibitors for Salmonella Typhi Produce Conflicting Results in in Silico and in Vitro Studies

Detection of potential AcrAB-TolC multidrug efflux pump inhibitor in calyces extract of Hibiscus sabdariffa

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

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