In-vivo microscopy reveals the impact of Pseudomonas aeruginosa social interactions on host colonization

Abstract

Pathogenic bacteria engage in social interactions to colonize hosts, which include quorum-sensing-mediated communication and the secretion of virulence factors that can be shared as “public goods” between individuals. While in-vitro studies demonstrated that cooperative individuals can be displaced by “cheating” mutants freeriding on social acts, we know less about social interactions in infections. Here, we developed a live imaging system to track virulence factor expression and social strain interactions in the human pathogen Pseudomonas aeruginosa colonizing the gut of Caenorhabditis elegans. We found that shareable siderophores and quorum-sensing systems are expressed during infections, affect host gut colonization, and benefit non-producers. However, non-producers were unable to successfully cheat and outcompete producers. Our results indicate that the limited success of cheats is due to a combination of the down-regulation of virulence factors over the course of the infection, the fact that each virulence factor examined contributed to but was not essential for host colonization, and the potential for negative frequency-dependent selection. Our findings shed new light on bacterial social interactions in infections and reveal potential limits of therapeutic approaches that aim to capitalize on social dynamics between strains for infection control.

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Data availability

All raw data sets have been deposited in the Figshare repository (https://doi.org/10.6084/m9.figshare.8068715.v1).

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Acknowledgements

We thank two anonymous reviewers for constructive comments and the Center of Microscopy and Image Analysis (University of Zürich) for support with image acquisition and advice on image analysis.

Funding

This project has received funding from the Swiss National Science Foundation (grant no. PP00P3_165835 and 31003A_182499 to RK and no. P2ZHP3_174751 to ETG), and the European Research Council under the grant agreement no. 681295 (to RK).

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Correspondence to Chiara Rezzoagli or Rolf Kümmerli.

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