Outer membrane permeability of mcr-positive bacteria reveals potent synergy of colistin and macromolecular antibiotics against colistin-resistant .

Colistin (CT) is the last-resort of antibiotic against multidrug-resistance (MDR) () infection. However, colistin resistance is increasingly reported in isolates partially due to the global emergence and dissemination of plasmid-borne mobile colistin resistance () gene and is a threat to human health. Thus, available treatment strategies urgently required in the fight against colistin-resistant . Here, we showed that confers damaged outer membrane (OM) permeability in , which could compromise the viability of . Consistently, with colistin resistance exhibits increased susceptibility to macromolecular antibiotics such as rifampicin (RIF) and erythromycin (ERY). Moreover, the combination therapy of colistin and rifampicin demonstrates efficacy against colistin-resistant , regardless of the presence of . Altogether, our data suggest that the synergy of colistin in combination with macromolecular hydrophobic antibiotics poses a promising therapeutic alternative for colistin-resistant .