Feeding your enemy's enemy: Acidifying bacteria inhibit pathogenic bacteria more strongly with increasing glucose

Abstract

Classical microbiology has focused on directly suppressing pathogens using drugs, ignoring other harmless microbial species living alongside the pathogens. We now have a much better understanding of how species interact and affect one anothers growth within microbial communities, for example through chemical production. Here we capitalize on this understanding to demonstrate how one can manipulate and control the strength of interactions between bacterial species, and combine this with antibiotics to fully suppress and eliminate pathogens. Using experiments and a mathematical model, we first show how Citrobacter freundii can reduce the environmental pH to enhance the effect of ampicillin on the pathogen Pseudomonas aeruginosa. This negative interaction from C. freundii to P. aeruginosa can be strengthened by increasing glucose concentrations. Our proof-of-concept approach also worked against other pathogens: Klebsiella pneumoniae and Agrobacterium tumefaciens, and a different commensal: Lactobacillus plantarum, a common probiotic species. Overall, we show that taking advantage of the community and chemical context in which microbes live can help to develop efficient strategies to control them. In the medical context, this approach can help to eliminate pathogens thereby reducing our reliance on antibiotics.