In-vivo microscopy reveals the impact of Pseudomonas aeruginosa social interactions on host colonization
Chiara Rezzoagli1,2, Elisa T Granato3, Rolf Kümmerli4,5
1Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland. chiara.rezzoagli@uzh.ch.
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.
Insights
Cooperative bacteria use public goods like siderophores during infection. Cheating mutants, however, struggle to outcompete producers in Pseudomonas aeruginosa gut colonization, limiting therapeutic strategies.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Social Behavior
Background:
- Pathogenic bacteria exhibit social behaviors, including quorum sensing and public goods secretion, crucial for host colonization.
- In vitro studies show cooperative bacteria can be outcompeted by 'cheating' mutants, but in-vivo dynamics are less understood.
- Understanding bacterial social interactions during infection is vital for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate bacterial social interactions and virulence factor expression in Pseudomonas aeruginosa during Caenorhabditis elegans gut colonization.
- To determine the impact of shareable public goods and quorum sensing on host colonization and strain competition.
- To elucidate the factors limiting the success of cheating mutants in an infection setting.
Main Methods:
- Development of a live imaging system to track bacterial behavior and gene expression in real-time.
- Monitoring virulence factor expression (siderophores) and quorum sensing systems during P. aeruginosa infection in C. elegans.
- Quantifying the colonization success and competitive interactions between cooperative and cheating bacterial strains.
Main Results:
- Shareable siderophores and quorum sensing systems are expressed during P. aeruginosa infections and benefit non-producers.
- Non-producer (cheating) mutants did not outcompete producer strains in C. elegans gut colonization.
- Limited success of cheats is attributed to virulence factor downregulation, non-essential nature of individual factors, and negative frequency-dependent selection.
Conclusions:
- Bacterial social dynamics, including public goods and quorum sensing, play a significant role in host colonization by P. aeruginosa.
- Cheating mutants face limitations in competitive success during infection, contrary to in vitro observations.
- Findings offer insights into bacterial social evolution in infections and potential constraints for social dynamics-based therapies.
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