LAUSR

Significance Natural products are important mediators in interacting microbial communities. Here, we show that bacteria can defend themselves against a common predator by teaming up. This form of cooperative defense relies on the production of a linear lipopeptide by a Pseudomonas species, which induces the production of peptidases and proteases in a Paenibacillus species. These enzymes degrade the lipopeptide into fragments which are highly toxic to the amoebal predator. Investigating microbial interactions enables identification of novel chemical entities with potent biological functions. Bacteria are inherently social organisms whose actions should ideally be studied within an interactive ecological context. We show that the exchange and modification of natural products enables two unrelated bacteria to defend themselves against a common predator. Amoebal predation is a major cause of death in soil bacteria and thus it exerts a strong selective pressure to evolve defensive strategies. A systematic analysis of binary combinations of coisolated bacteria revealed strains that were individually susceptible to predation but together killed their predator. This cooperative defense relies on a Pseudomonas species producing syringafactin, a lipopeptide, which induces the production of peptidases in a Paenibacillus strain. These peptidases then degrade the innocuous syringafactin into compounds, which kill the predator. A combination of bioprospecting, coculture experiments, genome modification, and transcriptomics unravel this novel natural product-based defense strategy.