NSF-BSF: Unraveling Interspecies Communication between Microbes that Colonize Humans

With the support of the Chemistry of Life Processes program in the Division of Chemistry, Professor Yftah Tan-Gan from the University of Nevada, Reno and Professor Michael Meijler from Ben-Gurion University of the Negev are investigating the chemical interactions that bacteria utilize to communicate between each other. Bacterial species employ a variety of chemical signals to assess their surroundings and modify their behavior in response to environmental changes. This process is called quorum sensing. Since many bacterial species occupy the same environmental niches, including inside the human host, identifying the chemical crosstalk between different bacterial species and between bacteria and the host is pivotal. This study identifies the chemical signals and the target proteins involved in communication among bacterial species that colonize humans, providing critical insight as to how bacteria coordinate colonization and other population-wide processes and laying the foundation to control and alter bacterial behavior. Undergraduate and graduate students involved in this project acquire specialized training in both chemistry and microbiology, from synthetic chemistry and chemical proteomics to microbiology. This project involves an international collaboration that brings together the PI’s expertise in developing peptide-based signal modulators with the collaborator’s expertise in bacterial communication and chemical proteomics to allow cross-training of students in different chemical biology techniques. This interdisciplinary project is aimed at identifying the chemical interactions between Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus oligofermentans. These species are prevalent members of the microbiota that often encounter each other inside the human host. To this end, traditional microbiological methods will be integrated with chemical biology techniques involving synthetic peptides, photoactivatable probes, and chemical proteomics to pursue the following objectives: 1) determine the effects of signaling molecules from E. faecalis, S. aureus, P. aeruginosa and S. oligofermentans on the behavior of one another; 2) identify receptors for these signals among the affected bacteria; and 3) examine the roles of these receptors to unravel how each of these species reacts and adjusts their behavior to the presence of the other bacteria. 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.