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Quorum sensing evolution and function in mixed bacterial communities

$433,459R35FY2025GMNIH

University Of Kansas Lawrence, Lawrence KS

Investigators

Abstract

PROJECT SUMMARY Bacteria – both beneficial and harmful – are primarily found in complex communities where they engage in intricate social interactions with profound implications for human health. The focus of our work is on a type of bacterial interaction involving cell-cell communication called quorum sensing, which is used by many bacteria to coordinate group activities. Quorum sensing regulates virulence in many common pathogens and is used as a model to explore general features of bacterial communication and cooperation in a broader sense. Prior studies of quorum sensing have provided a mechanistic basis for understanding how these systems function in monocultures; however, there remains a major gap in understanding the role of quorum sensing in mixed microbial communities and dynamically changing populations. Such information will inform efforts to manipulate quorum sensing as an anti-infective strategy and is fundamental to quorum sensing biology. The PI has developed laboratory `synthetic ecological' models to study quorum sensing in mixed populations. These models have enabled rigorous molecular- and population-level studies of the behavior and evolution of quorum sensing. Results of our studies over the past five years have highlighted the crucial role of quorum sensing in mixed-strain and mixed-species environments and demonstrated that quorum sensing functions differently in different strains. These studies also showed that quorum sensing enables “eavesdropping” on the quorum sensing signals of other bacteria. The overarching goal of this MIRA program is to combine our laboratory models with molecular genetic and genomic approaches to expand our understanding of quorum sensing in complex environments; from studies within individual strains with different genetic backgrounds to studies of interactions between different strains and between different species. The proposed studies focus on three future goals, which are to: 1) define how genetic adaptations alter quorum sensing regulation of antibiotic resistance; 2) determine how different quorum sensing architectures influence cooperative interactions between different strains; and 3) understand how bacteria use quorum sensing to eavesdrop on competitors. Results of the proposed experiments will advance knowledge of quorum sensing and how bacteria behave in complex communities, and ultimately inform efforts to target quorum sensing as an anti-virulence strategy.

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