Biogeography of Microbial and Plant-Derived Redox-Active Small Molecules and Combinatorial Effects on Microbial Growth - Biogeography of Microbial and Plant-Derived Redox-Active Small Molecules and Combinatorial Effects on Microbial Growth Soil is the source for many antibiotics of clinical relevance and the training ground for the organisms that both produce and resist them. Engineering and managing microbial communities in human health necessitates an understanding of the soil environment where these organisms often originate. My lab is working to determine the combinations of plant and microbial small molecules that microbial communities experience in soils and how this affects their growth and survival across environments. It is now evident that antibiotics produced by soil bacteria and their co-occurring microbial neighbors can shape microbial growth as well as community composition, function, and resilience. However, we do not yet understand the biogeography of these small molecules, i.e. what combinations of natural antibiotics a microbe might typically encounter and how this varies from one microbial community to another. In addition, much work has focused on studying microbe-microbe interactions facilitated by small molecules. Yet, in soils, microbial consortia often live on plant hosts that release natural products capable of sculpting rather than eliminating the microbial community. How does this work? While some plant secondary metabolites do inhibit canonical antibiotic targets (ribosomes, DNA replication, cell wall biosynthesis), many plants also produce low-dose antimicrobial compounds that use reduction-oxidation (redox) reactions to control microbial communities at their roots. We suggest i) that root-associated microbial communities offer an experimentally tractable system to test hypotheses about secondary metabolite biogeography ii) that the production of plant and microbial redox-active metabolites is an expedient entry point for these studies and iii) that plant-produced redox-active metabolites have been understudied as features of the soil environment that may offer insights into how microbes have learned to survive in diverse contexts, including infections. This proposal outlines my lab’s long-term plan to study the patterning and combinatorial physiological effects of microbial and plant redox-active compounds on the growth and development of microbial communities. We will take a two-pronged approach. The first part of our efforts will be aimed at using newly developed screens to identify redox-active metabolites made natively in soils and determine patterns of (co)production. A second area of our work will explore the molecular mechanisms by which known redox-active plant metabolites (coumarins) affect microbes. Iteration between the two approaches will allow us to conduct environmentally informed experiments that test the effects of co-occurring small molecules on microbial communities. Findings from this work will inform the development of therapeutics to irradicate microbial infections and provide tools for the discovery and activation of novel antimicrobial compounds produced by soil organisms.
