Sublethal colistin exposures prime multidrug-resistant Gram-negative pathogens for enhanced predation by Bdellovibrio

Predatory bacteria offer a distinct strategy against antimicrobial-resistant Gram-negative pathogens, but their interactions with antibiotics remain poorly defined. Bdellovibrio bacteriovorus HD100 remained viable during colistin exposure and synergized with colistin against mcr-1 -positive Escherichia coli . At 8 mg/L colistin and a predator-to-prey ratio of approximately 1.5, combination treatment produced a 6.75-log reduction in viable prey by 6 h, reduced counts below detection by 24 h, and depleted qPCR-detectable mcr-1 abundance by 99.96%. Transient colistin pretreatment increased HD100 attachment twofold and bdelloplast formation 1.56-fold. Colistin increased prey outer-membrane permeability without detectable inner-membrane disruption, whereas polymyxin B nonapeptide, a markedly weaker bactericide, reproduced the predation-enhancing effects. Potentiation extended to Gram-negative pathogens, including Klebsiella pneumoniae and Acinetobacter baumannii . In Galleria mellonella , combination treatments increased day-3 survival to 50%, compared with 0%, 8.3%, and 16.7% for untreated, colistin, and HD100 groups, respectively. These findings define antibiotic-facilitated predation as a strategy exploiting residual antibiotic activities against pathogens.