Chen, Z.; Wingreen, N. S.; Gitai, Z.

Microbial competition shapes polymicrobial communities, yet it remains unclear whether bacteria deploy fixed or specific antagonistic strategies against different rivals. Here we show that Pseudomonas aeruginosa deploys distinct strategies to outcompete two clinically relevant species, Burkholderia cenocepacia and Staphylococcus aureus. Under matched conditions, competition with B. cenocepacia is mediated by contactdependent Type VI secretion, whereas competition with S. aureus follows a staged diffusible program of alkyl quinolone-mediated growth inhibition followed by LasA-dependent lysis. Transcriptomic analysis supports a "Swiss Army knife" model of antagonism in which different competitive context triggers distinct subsets of P. aeruginosa's arsenal. Minimal dynamical models verify that contact-dependent killing is effective against slower-growing competitors, whereas a staged strategy of growth inhibition followed by killing via diffusible factors is preferable against faster-growing rivals. Together, these results show that the competitive success of P. aeruginosa depends on competitor-specific antagonistic strategies.