1-benzyl-1,4-diazepane reduces the efflux of resistance-nodulation-cell division pumps inEscherichia coli

Year: 2020

Authors: Casalone E., Vignolini T., Bracono L., Gardini L., Capitanio M., Pavone F.S., Dei S., Teodori E.

Autors Affiliation: Univ Florence, Dept Biol, Via Madonna del Piano 6, I-50019 Sesto Fiorentino, Italy; LENS European Lab Nonlinear Spect, Via Nello Carrara 1, I-50019 Sesto Fiorentino, Italy; Dept Neurosci Psychol Drug Res & Child Hlth NEURO, Via U Schiff 6, I-650019 Sesto Fiorentino, Italy; CNR, Natl Inst Opt, Largo Fermi 6, I-50125 Florence, Italy; Univ Florence, Dept Phys & Astron, Via Sansone 1, I-50019 Sesto Fiorentino, Italy.

Abstract: Aim: To investigate the action mechanism of 1-benzyl-1,4-diazepane (1-BD) as efflux pump inhibitor (EPI) in Escherichia coli mutants: ΔacrAB or overexpressing AcrAB and AcrEF efflux pumps. Materials & methods: Effect of 1-BD on: antibiotic potentiation, by microdilution method; membrane functionality, by fluorimetric assays; ethidium bromide accumulation, by fluorometric real-time efflux assay; AcrB expression, by quantitative photoactivated localization microscopy. Results: 1-BD decreases the minimal inhibitory concentration of levofloxacin and other antibiotics and increase ethidium bromide accumulation in E. coli overexpressing efflux pumps but not in the ΔacrAB strain. 1-BD increases membranes permeability, without sensibly affecting inner membrane polarity and decreases acrAB transcription. Conclusion: 1-BD acts as an EPI in E. coli with a mixed mechanism, different from that of major reference EPIs.

Journal/Review: FUTURE MICROBIOLOGY

Volume: 15 (11)      Pages from: 987  to: 999

More Information: This work was supported by Fondazione CR Firenze (grant numbers 2016.1086, 2017.0750, 2017.0827); the European Union´s Horizon 2020 research and innovation program grant no. 654148 Laserlab-Europe and by EMPIR project MetVBadBugs 15HLT01. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
KeyWords: Multidrug resistance; MDR; E. coli; efflux-pump inhibitor; EPI; levofloxacin potentiation; membrane permeability; AcrAB expression
DOI: 10.2217/fmb-2019-0296

ImpactFactor: 3.165
Citations: 7
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