Quorum Sensing Across Scales and Between Domains

Harmful bacteria have the capacity to kill humans, animals, and plants, while beneficial bacteria play vital roles in keeping humans, animals, and plants alive. To accomplish these powerful feats, bacteria communicate with chemical molecules, count their numbers, and act as collectives. This process of cell-to-cell communication in bacteria is called “Quorum Sensing” and it allows bacteria to synchronize behavior on a population-wide scale. This project aims to study quorum sensing control of bacterial behavior. The discoveries of this project could yield quorum-sensing targets that are vulnerable to synthetic intervention; these interventions could be used to control pathogens or eradicate undesirable bacterial communities in medical and industrial contexts, or alternatively, to promote beneficial bacteria in the human gut microbiome or foster community formation for bioremediation efforts. Activities such as student training, STEM education and public outreach will be major components of this project. Quorum sensing is a bacterial communication process that relies on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. Quorum sensing enables groups of bacteria to collectively alter behavior in response to changes in population density and species composition of the vicinal community. Aim 1: From the molecule to the network to the cell combines chemical, genetic, and phenotypic strategies to discover how quorum-sensing control of phage-phage and phage-host interactions dictates prophage fates during polylysogeny. The work will expand knowledge of the stimuli that phages can monitor, reveal how phage and host quorum-sensing communication shapes parasite-host interactions, and contribute foundational principles to the new and burgeoning field of cross-domain chemical communication. Aim 2: From the cell to the community of cells will use genetics, imaging, and biophysical theory to define mechanisms by which quorum sensing and three-dimensional morphogenesis interact in space and time to drive bacterial community maturation. The studies will deliver the first high-resolution spatiotemporal map that defines the relationships between local material parameters, quorum-sensing-mediated cell-cell communication, and three-dimensional community morphology. The output of the proposed research could create a paradigm for the types of multiscale investigations required to make transformative progress in similarly complex systems. Insights garnered from the proposed quorum-sensing research is fundamental to all of microbiology, including basic, clinical, industrial, and ecological microbiology and could prove key to advancing the general understanding of collective behaviors among cells, including those of higher organisms. Furthermore, an important practical aspect of these investigations is the development of strategies to inhibit or promote quorum sensing on demand that can be used for societal applications that are urgently needed in medical, industrial, and ecological contexts. 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.