Toward engineered microbiomes: Understanding cooperativity in microbial communities (Section II.A.1.a.iii.3 Microbiology)
Abstract
Microorganisms play a central role in our lives. The majority are members of microbial communities which profoundly influence our well-being. These microbiomes play a role in health, ecology, energy, and agriculture. For example, the commensals that reside in the intestinal tract are essential in development, pathogen protection, and digestive health. Overall, these important functions, which are mediated by the community as whole, are the result of an intricate synergy among the member cells. There exists a fundamental knowledge gap between our molecular-scale understanding of in vitro bacterial biochemistry and the community-level knowledge gleaned from discovery-based biochemical approaches. We aim to bridge this gap by imaging the spatial and metabolic relationships between microbiome members at the single-cell and single-molecule level. In the long run, by bringing live-cell biophysics approaches to the context of microbiomes, we will begin to controllably engineer microbiomes based on environment, for instance via prebiotic nourishment. Our objective is to determine the guiding principles by which mixed microbial communities are organized and how this organization is communicated and maintained. Though the makeup of a microbiome ensures its function, changes in available metabolites can alter the overall microbiome composition and cause an irreversible decrease in species diversity. These changes are mediated at the community level by intercellular signaling, and at the molecular scale by outer-membrane protein reorganization. We hypothesize that the energetics and dynamics of these responses infer resistance to change-and thus adaptability-upon a microbial community, and that understanding these responses will enable controllable engineering of communities. Here, we will measure the assembly and response of cells in two important members of the human gut community: Bacteroides thetaiotaomicron (Bt) and Ruminococcus bromii (Rb). These bacteria are key players in carbohydrate catabolism: Bt is prevalent in the gut and has very well characterized and highly regulated starch utilization (Sus)-like protein systems for carbohydrate catabolism, while Rb is a "keystone" species that enables the existence of other community members in the gut. For instance, Bt can grow on byproducts of the digestion of resistant starch and dietary fiber by Rb. We will: (1) Measure the spatial relationships between bacterial species in a mixed community. (2) Control the spatial relationships between bacterial species in a mixed community. (3) Visualize and characterize intercellular cross-feeding in a mixed community. Overall, by measuring the single-cell enzymatic response as a function of spatial patterning in the microbiome, we will determine how changes in expression are signaled and whether population-level changes arise from changes at the cell or assembly level. These studies will broadly impact our molecular-scale understanding of how bacteria function in an ecosystem: ultimately, by precisely defining the nanoscale roles of each member of a microbial community, we will understand the complex function of the microbiome. Moreover, the work in this proposal has specific relevance to the ARO Microbiology Program, as a mechanistic understanding of how individual cells function within a microbiome will enable us to affect change in these communities. Using the Bt/Rb model system to capture the dynamic response of bacteria to fluctuating nutrients will allow us to develop a general model to explain how microbes cooperate and compete across diverse ecosystems and the experimental advances will provide methods for imaging living anaerobic cells. These advances in our knowledge will lead to better health for soldiers and better maintenance of military material.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 14, 2019
- Source ID
- W911NF1810339
Entities
People
- Julie S. Biteen
Organizations
- Army Contracting Command
- United States Army
- University of Michigan