Most bacteria naturally congregate to form complex communities called biofilms through an elaborate process that involves secretion of a thick, gooey substance that allows cells to stick to each other and to surfaces, thus providing the community with protection against harsh environments, other bacteria and predators, and antibiotics. These biofilms are abundant in natural environments and play an important role in many clinical, industrial, and ecological settings. For example, bacterial biofilms found in rivers and lakes are critical components of food chains; biofilms in oil and gas pipelines can lead to severe corrosion problems; biofilms associated with agricultural crops can either cause disease or be beneficial to plants; and biofilms in hospitals contribute significantly to risk of infection transmission and to the staying power of infections. Due to the ubiquity and significant impacts of biofilms on human activities, there is a clear need to better understand how these biofilms develop. This project will investigate a critical but poorly understood aspect of biofilms: the role that the most important general reactions of the cell (called central metabolism) play during biofilm development. This project will provide the first in depth investigation of how the general reactions in a cell change during bacterial biofilm formation, and has the potential to fundamentally transform our understanding of what really happens to cells when they join a biofilm community and how we might be able to encourage or interfere with biofilm formation. In addition, this project will have significant broader impacts on education through the participation of graduate and undergraduate students in research activities and training, as well as through outreach activities that foster enthusiasm for the field of microbiology.
The overarching hypothesis in this project is that dynamic remodeling of central carbon and nitrogen metabolism constitutes an essential component of the highly coordinated physiological response that takes place during biofilm development. Using Bacillus subtilis as a model organism, the work will integrate state-of-the-art systems-level metabolomic and proteomic approaches, microscopy, and quantitative computational modeling, to generate the following outcomes: 1) a systems-level quantitative understanding of how metabolism is remodeled during biofilm formation; 2) elucidation of driving regulatory mechanisms controlling metabolic remodeling during biofilm formation; 3) novel insights regarding metabolic heterogeneity within biofilm cell subpopulations; and 4) elucidation of the physiological relevance of major metabolic alterations during biofilm development. These results will significantly advance the understanding of the underlying logic and unifying principles behind the complex signaling systems of the biofilm regulatory network and will provide a holistic and quantitative understanding of the role of metabolism in biofilm development.