Contact-dependent growth inhibition drives kin discrimination and shapes in vivo strain dominance in Pseudomonas aeruginosa infection
Year: 2026
Type: preprint
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. Author Summary Bacterial populations frequently consist of diverse strains competing for the same resources and spatial niche. We investigated how a form of interbacterial competition called contact-dependent growth inhibition (CDI) contributed to fitness and survival among diverse strains of Pseudomonas aeruginosa . Our findings demonstrate that bacteria deploy these contact-dependent weapons to distinguish self from non-self, governing complex competitive relationships that range from aggressive offensive killing to specialized defensive protection. Finally, using a mouse model of acute pneumonia, we confirmed that CDI actively dictates strain dominance and shapes overall bacterial burdens during infection. Together, our work shows that CDI acts as a vital mechanism for strain discrimination, directly driving population structure and strain succession in complex environments.
Institutions: Loyola University Chicago, Loyola Medicine
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W7218914280