Bacteria synthesize and release specific chemicals that signal to the local microbial population that it has reached a level sufficient to change their behavior from acting as individual cells to a multicellular mode. The bacterial population is said to reach a quorum level and the signaling chemicals are called Quorum Sensing (QS) signals. When a quorum population is achieved, bacteria turn on cooperative, "group-beneficial" social traits that include biofilm formation (for example plaques on teeth), toxin secretion and development of resistance to antibiotics. The specificity in QS signals made by the enzyme acyl-homoserine lactone (AHL) synthase requires that this protein selectively recognizes and reacts with a specific helper protein (an acylated acyl-carrier protein) to avoid creating non-specific signals. With this award, the Chemistry of Life Processes is funding Dr. Rajesh Nagarajan at Boise State University to investigate the molecular interactions of the carrier protein and AHL synthase that direct the synthesis of correct quorum sensing signals. This project utilizes a combination of biochemistry, enzymology and nuclear magnetic resonance (NMR) tools to determine the molecular details for how two different AHL synthases selectively recognize native over non-native compounds for the acyl-carrier protein. Results from this study help guide the design of quorum sensing specific inhibitors as potential ways to disrupt bacterial growth. The educational plan of this project provides interdisciplinary training in cutting-edge research for high school, undergraduate and graduate students and integrates evidence-based research methods into the laboratory curriculum. The plan for outreach engages low-income, rural and first-generation college students at Boise State University in research, and offers a hands-on, direct research opportunities for high school science teachers in the laboratory. This project helps to connect Dr. Nagarajan's laboratory with local high school science teachers and high school classrooms to encourage students to consider careers in STEM disciplines.
Acyl carrier proteins serve as indispensable cofactors in several primary and secondary metabolic pathways that include the biosynthesis of fatty acids, polyketides, quorum sensing signals and nonribosomal peptide natural products. In general, the molecular basis on how acyl carrier proteins are able to interact with a multitude of enzyme partners and yet retain specificity for each enzyme is a poorly understood research area. This project addresses how two different AHL synthases recognize their cognate carrier proteins to impart fidelity in quorum signal synthesis. The methodology used in this study should open new doors for a broader investigation on differences in carrier protein recognition between enzymes involved in primary and secondary metabolism. Finally, small molecules that interrupt intercellular communication could also serve as useful chemical probes to investigate the social communication among bacterial communities.
This project is jointly funded by the Chemistry of Life Processes (CLP) program of the Chemistry Division, the Established Program to Stimulate Competitive Research (EPSCoR), and Office of Multidisciplinary Activities (OMA) in the Mathematical and Physical Sciences (MPS) Directorate.
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.
