21Antimicrobial combinations have been proven to be a promising approach in the 22 confrontation with multi-drug resistant bacterial pathogens, owing to enhancement of 23 antibacterial efficacy, deceleration of resistance development rate and mitigation of side 24 effects by lowering the doses of two drugs. In the present study, we report that combination 25 of furazolidone (FZ) and other nitrofurans with a secondary bile salt, Sodium Deoxycholate 26 (DOC), generates a profound synergistic effect on growth inhibition and lethality in 27 enterobacteria, including Escherichia coli, Salmonella, Citrobacter gillenii and Klebsiella 28pneumoniae. Taking E. coli as the model organism to study the mechanism of DOC-FZ 29 synergy, we found that the synergistic effect involves FZ-mediated inhibition of efflux pumps 30 that normally remove DOC from bacterial cells. We further show that the FZ-mediated nitric 31 oxide production contributes to the synergistic effect. This is to our knowledge the first report 32 of nitrofuran-DOC synergy against Gram-negative bacteria. 33
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