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

Abstract

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.

The ins and outs of RND efflux pumps in Escherichia coli

“…A similar result was obtained when MDR E. coli of animal origin was assessed wherein NMP was able to reverse resistance to ciprofloxacin, tetracycline and florfenicol. However, NMP showed to be inefficient in reversing resistance to ampicillin ( Marchetti et al, 2012 ).…”

Exposure to Sub-inhibitory Concentrations of the Chemosensitizer 1-(1-Naphthylmethyl)-Piperazine Creates Membrane Destabilization in Multi-Drug Resistant Klebsiella pneumoniae

“…1-(1-Naphthylmethyl)-piperazine was reported to reverse MDR in Acinetobacter baumannii (Pannek et al, 2006), Vibrio cholerae (Bina et al, 2009), Staphylococcus aureus (Li et al, 2011), E. coli (Kern et al, 2006), Citrobacter freundii, Enterobacter aerogenes , and Klebsiella pneumoniae (Schumacher et al, 2006). When used as an adjuvant, NMP reversed bacterial resistance against several compounds including dyes, phenicol-based drugs, fluoroquinolones, rifampicin, linezolid, tetracyclines, and others (Bohnert and Kern, 2005; Kern et al, 2006; Schumacher et al, 2006, 2007; Li et al, 2011; Marchetti et al, 2012). Furthermore, NMP was also reported to inhibit the secretion of two virulence factors, the cholera toxin and the toxin-co-regulated pilus in Vibrio cholerae (Bina et al, 2009).…”

Tissue depletion of doxycycline after its oral administration in food producing chicken for fattening

“…12 Additionally, bacterial populations do not respond to traditional treatments commonly used for human illnesses. 13 The antibiotics' residue levels reached in organs and the rate of their depletion from tissues depend on the method of administration, animal species, as well as dose and specific formulation of a given drug. The differences in the antibiotic concentration and time of its depletion may also be influenced by the differences in the intake of drinking water by animals as well as its quality.…”