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bioRxiv · 10.64898/2026.09.30.755834

Contact-dependent growth inhibition drives kin discrimination and shapes in vivo strain dominance in Pseudomonas aeruginosa infection

Peterson, N.·Cobe, B.·Bronson, A.·Allen, J.
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Abstract

Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an opportunistic pathogen. Rather than existing as single clonal lineages, environmental and clinical populations often consist of a mixture of distinct strains that directly compete to dominate the niche. To eliminate rivals, P. aeruginosa deploys a form of interference competition termed contact-dependent growth inhibition (CDI). CDI is mediated by CdiA, where, upon cell contact, the CdiA C-terminal toxin domain is delivered to prey cells. Toxin-producing cells encode for a cognate CdiI immunity protein to prevent self-intoxication. Different strains of P. aeruginosa encode for CdiA proteins with different C-terminal toxin domains and cognate CdiI immunity proteins. Most studies have relied on engineered strains to investigate the mechanism of CDI. While extremely useful for studying CdiA-mediated intoxication, such work masks the true diversity of wild-type CdiA variants and their impact on competitive interactions between strains. In this study, we systematically investigated CDI-mediated competition using unique conspecific strains of P. aeruginosa. We identified several novel CdiA toxin domains and mapped the competitive outcomes they govern. Furthermore, using a mouse model of acute pneumonia, we demonstrate that CDI-mediated interference competition actively occurs during mixed-strain infections in vivo. Together, our findings reveal that P. aeruginosa leverages CDI as a potent, strain-dependent kin discrimination mechanism that directly shapes population dynamics and strain dominance within host and natural environments.

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Peterson, N., Cobe, B., Bronson, A., Allen, J.. 2026-10-02. Contact-dependent growth inhibition drives kin discrimination and shapes in vivo strain dominance in Pseudomonas aeruginosa infection. https://doi.org/10.64898/2026.09.30.755834

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