DOI: 10.1101/518050Jan 11, 2019Paper

In vitro synergy between Sodium Deoxycholate and Furazolidone against Enterobacteria via Inhibition of Multidrug Efflux Pumps

BioRxiv : the Preprint Server for Biology
Vuong Van Hung LeJasna Rakonjac

Abstract

Antimicrobial combinations have been proven to be a promising approach in the confrontation with multi-drug resistant bacterial pathogens, owing to enhancement of antibacterial efficacy, deceleration of resistance development rate and mitigation of side effects by lowering the doses of two drugs. In the present study, we report that combination of furazolidone (FZ) and other nitrofurans with a secondary bile salt, Sodium Deoxycholate (DOC), generates a profound synergistic effect on growth inhibition and lethality in enterobacteria, including Escherichia coli, Salmonella, Citrobacter gillenii and Klebsiella pneumoniae. Taking E. coli as the model organism to study the mechanism of DOC-FZ synergy, we found that the synergistic effect involves FZ-mediated inhibition of efflux pumps that normally remove DOC from bacterial cells. We further show that the FZ–mediated nitric oxide production contributes to the synergistic effect. This is to our knowledge the first report of nitrofuran-DOC synergy against Gram-negative bacteria.

Related Concepts

Klebsiella pneumoniae
Bile Salts
Enterobacteriaceae
Escherichia coli
Furazolidone
Gram-Negative Bacteria
Nitric Oxide
Nitrofurans
Deoxycholic Acid, Monosodium Salt
Deoxycholate

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