PROJECT SUMMARY Bacterial cells communicate through the language of molecular cues that are released into the environment and detected by cells in nearby communities. While prevalent in every ecological niche, pathogenic bacteria may exploit this molecular crosstalk to survive stress conditions, escape immune detection, and evade the action of antibiotics. This project will investigate how molecules that are derived from the bacterial cell wall regulate bacterial growth decisions using the paradigm of bacterial dormancy in a prototypic uropathogenic strain of Escherichia coli. This research will identify the pharmacophore of the cell wall signal, or cue, elucidate genes that enable the bacterial response to the signal, and identify bacterial protein targets that engage the signal to further understand the underlying mechanism of bacterial crosstalk. We propose an innovative, multifaceted approach to understand this bacterial crosstalk by combining research methods in synthetic chemistry, bacterial genetics, and ligand-capture proteomics. During the course of this work, we will train undergraduate students majoring in Chemistry, Cell and Molecular Biology, and Biomedical and Pharmaceutical Sciences at Salve Regina University, a primarily undergraduate institution (PUI), and the University of Rhode Island, a collaborating institution. This training provides experiential learning objectives for undergraduate students, exposes them to biologic-based interdisciplinary research, and promotes strong collaboration between faculty at Salve Regina University, a PUI, and the University of Rhode Island, a research-intensive institution, thus strengthening the research environment of Salve Regina University.

Project Narrative Bacterial cells in the environment communicate through the language of molecular cues. Here, we propose to study how molecules derived from the bacterial cell wall regulate bacterial growth decisions using the paradigm of bacterial dormancy in a prototypic uropathogenic strain of Escherichia coli. This research will identify the pharmacophore of the cell wall signal, or cue, elucidate genes that enable the bacterial response to the signal, and identify bacterial protein targets that engage the signal to further understand the underlying mechanism of bacterial crosstalk. The work in this proposal will expose 6 to 10 undergraduate students to biomedically relevant research with significant impact in synthetic chemistry and bacterial genetics.