The contribution of novel cytidine deaminase regulatory systems to bacterial evolution

This project builds on the Waters laboratory's established expertise in bacterial chemical signaling to investigate the contribution of novel cytidine deaminase regulatory systems to bacterial evolution. The Waters lab has focused on understanding how signaling networks such as the second messenger cyclic di-GMP (c-di-GMP) and quorum sensing coordinate behaviors central to pathogenesis, including biofilm formation and virulence factor expression. Leveraging that foundation, this study examines how cytidine deaminase-linked regulatory elements may interface with existing signaling circuits to influence genetic and phenotypic adaptation in bacterial populations.

The Waters laboratory brings a perspective shaped by key observations about regulatory complexity in Vibrio cholerae: the presence of many enzymes with GGDEF, EAL, or HD-GYP domains that synthesize or degrade c-di-GMP, and the interplay between c-di-GMP and quorum sensing in controlling biofilm dynamics. From this starting point, the current project explores whether novel cytidine deaminase systems act as regulatory modulators that alter intracellular signaling states, thereby shaping evolutionary trajectories. The research frames cytidine deaminase regulatory systems not as isolated enzymatic activities but as potential contributors to regulatory networks that tune signaling molecules and gene expression programs under changing environmental conditions.

A central rationale for the work is that bacterial adaptation and the emergence of traits related to virulence and persistence are often governed by integrated regulatory systems rather than single pathways. By situating cytidine deaminase activity within the broader context of c-di-GMP-based signaling and quorum sensing, the study seeks to clarify mechanisms by which regulatory variation can produce heritable changes in behavior and fitness. The Waters lab's prior focus on identifying the cues that modulate the enzymatic activity of c-di-GMP synthesis and degradation proteins, and determining the specificity of those signaling pathways, positions it well to interrogate how cytidine deaminase regulators might influence or be influenced by those cues.

Outcomes of the project are expected to advance understanding of how regulatory modules contribute to bacterial evolution by modulating signaling networks that control communal behaviors such as biofilm formation and density-dependent gene regulation. Insights gained may elucidate pathways through which bacteria tune virulence and persistence, and may highlight novel regulatory intersections that can be targeted to disrupt harmful behaviors. Importantly, the project remains grounded in the Waters lab's translational perspective: because c-di-GMP and quorum sensing are promising targets for antimicrobial strategies, uncovering additional regulatory players, including cytidine deaminase systems, could inform future approaches to control bacterial disease.

Overall, this research integrates the Waters laboratory's deep knowledge of signaling specificity and regulatory complexity with a focused investigation into cytidine deaminase regulatory systems, aiming to reveal how such systems contribute to adaptive change in bacterial populations and to identify potential leverage points for therapeutic intervention.