Elucidating the Interplay between the ComRS and the ComABCDE Quorum Sensing Circuitries in Streptococci

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Professor Tal-Gan from the University of Nevada, Reno is studying how multiple communication pathways within the same species of bacteria affect bacterial behavior. Bacteria utilize a language of chemical signals to communicate with each other, assess their environment, and coordinate behavioral changes at the population level. Some bacterial species produce multiple chemical signals, each of which correspond to a different message and result in different behavioral responses. However, in some cases, two different signals can lead to a similar behavioral response through alternative communication pathways. The proposed study aims to characterize, at the molecular level, how different communication pathways within the same species of bacteria affect one another and consequently indirectly affect behaviors regulated by the other communication pathway. Understanding the interplay and hierarchy between different communication pathways could pave the way to manage and control bacterial behavior in diverse environmental niches. This study will allow undergraduate and graduate students to acquire specialized training in both chemistry and microbiology, from synthetic peptide chemistry and analytical characterization to microbiology and molecular biology techniques. This project also will be integrated into an outreach program aimed at providing undergraduate students and faculty from Lafayette College, a small liberal arts college in Easton, Pennsylvania, experience in hands-on research at the interface of chemistry and biology. This project aims to utilize Streptococcus mutans as a model system to study the interplay and hierarchy between the ComABCDE-like and ComRS quorum sensing circuitries at the molecular level. Competence for genetic transformation in streptococci is regulated by the competence regulon and relies on a cell-cell signaling mechanism, termed quorum sensing (QS). In some streptococci species the competence regulon is composed of a two-component-based QS circuit, termed the ComABCDE circuitry, while in other species, the competence regulon is composed of an RRNPP-type QS circuit, termed the ComRS circuitry. Importantly, some species of streptococci possess both a ComABCDE-like circuit and a ComRS-like circuitry. The proposed interdisciplinary project will integrate chemical biology techniques with traditional microbiology approaches to pursue the following objectives: 1) delineate the molecular mechanisms that govern the interplay between the ComABCDE-like and ComRS QS circuits in S. mutans; and 2) expand and generalize the rules governing the interplay between the ComABCDE-like and ComRS QS circuits to other bacterial species. 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.