CAREER: Designing Quorum Sensing Modulators for Lactobacillus plantarum to Probe Interspecies and Host-Microbe Interactions

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With the support of the Chemistry of Life Processes Program in the Division of Chemistry, Dr. Michael A. Bertucci of Moravian College is studying chemical signals that mediate cell-cell communication in bacteria present within the human body. These commensal bacteria do not cause infection. However, an imbalance in the presence or types of these bacteria has been linked to gastrointestinal disorders, gynecological disorders, and a greater susceptibility to infectious bacteria. Dr. Bertucci’s work focuses on a subset of these commensal microbes, known as lactic-acid bacteria, that regulate colony-wide communication through small peptides that serve as signals of bacterial density. The anticipated outcomes of this investigation include a novel method for synthesizing these peptides, the development of a library of peptide probes capable of enhancing or silencing lactic-acid bacteria cell-cell communication, and a greater understanding of how these communication pathways influence the positive health effects elicited by these bacteria. As a part of this interdisciplinary research program, planned education activities include a new course-based research experience and first-year research mentorship program at Moravian College, a primarily undergraduate institution that serves a significant population of first-generation and Pell-eligible students. Additional educational goals include leveraging social media to increase scientific engagement and literacy and establishing a science education training program for graduate and post-doctoral students seeking careers at teaching-focused institutions. The objective of this project is to synthesize and evaluate peptide-based modulators for the ubiquitous density-dependent chemical communication process known as bacterial quorum sensing (QS). The model system for this investigation is Lactobacillus plantarum (L. plantarum), a species with documented probiotic properties and a QS pathway controlled by a cyclic peptide (LamD). The stated objective will be accomplished by first studying the factors affecting peptide cyclization to develop a novel method for the synthesis of peptide thiolactones. Then, derivatives of native thiolactone LamD will be synthesized to conduct a series of systematic structure-activity scans in engineered L. plantarum mutants incapable of producing LamD. By harnessing this data, potent QS agonists and antagonists will be developed and employed to modulate QS in co-culture experiments to characterize the influence of QS on interspecies, intergenus, and host-microbe interactions. Completion of the described research objectives has the potential to advance understanding of the chemical basis for intercellular signaling in commensal bacteria, including how this signaling dictates ecological changes in mixed microbial populations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.