Genetic and Metabolic Determinants of Bacterial Interspecies Interactions

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Interspecies interactions are the foundation of bacterial community formation and function. Through their interactions, bacteria exert powerful influences on human health as commensal microflora, pathogens, biofilms, and antibiotic producers. A prevalent form of interaction among bacterial species relies on the exchange of specialized metabolites. Commonly represented by antibiotics, these bioactive metabolites function in myriad ways to promote the fitness of the producing species. Specialized metabolites may be toxic or growth inhibitory, or alternatively, they may function as signals and cues to relay information between species in a microbial community. Despite their importance for interactions between species, there is little understanding of the mechanisms that bacteria use to sense and respond to foreign specialized metabolites. This project focuses on an early-warning system for competitors, wherein bacteria detect specialized metabolites from other species and respond by activating a surface-mobile population. This example of an adaptive physiological response to a competitor provides the bacteria an opportunity to either escape or to counterattack. This project has two specific aims. The first aim is to define the mechanisms that activate and control bacterial motility when bacteria are exposed to specialized metabolites from a competitor. In particular, this aim will focus on major changes in metabolism and the controlling genetic functions that support a transition to a mobilized population. The second aim is to identify new motility-inducing metabolites produced by competing bacteria. Previously identified inducers are protein synthesis inhibitors that stimulate motility at subinhibitory concentrations. New inducers of unknown structure will be identified from different strains of bacteria. These inducers will expand knowledge of chemical forms that induce surface mobilization and will function as chemical probes to understand the pathways to activating the mobile response. Because inducers include protein synthesis inhibitors, new candidate antibiotics may be identified among the target specialized metabolites. Overall, these studies will advance understanding of specialized metabolism in dynamic interactions between bacterial species and how a mobile response promotes competitive fitness.