The antihelminthic salicylanilides are not only just act as adjuvants in combination with colistin

Background:The depletion of the antibiotic development pipeline, in addition to increasing antimicrobial resistance, has prompted the search for adjuvants that can interfere with bacterial resistance. Objectives:In the combination of salicylanilides and colistin, we aimed to:(1) demonstrate salicylanilides act as antimicrobial agents but not just adjuvants, (2) determine key genes that mediate Gram-negative bacterial (GNB) resistance to salicylanilides, (3) propose that the mechanism of bactericidal action of salicylanilides may not be directly related to the dissipation of proton motive force (PMF) and inhibition of ATP production. Methods:The checkerboard assay was used to demonstrate the role of salicylanilides in antimicrobial combinations. We obtained salicylanilides-sensitive bacteria by gene editing. Oxidative phosphorylation of salicylanilides detected by fluorescence assay. We used a meta-transcriptomic approach in an effort to understand the the underlying mechanism of closantel against GNB.