EAGER: Investigating a Trojan Horse strategy to disrupt Saccharomyces biofilms

Microbes are single-celled organisms found nearly everywhere on earth and are intricately involved in the functioning of biological systems. Most microbes live in complex communities and engage in social interactions ranging from cooperation to lethal warfare. One type of cooperation occurs when individual microbes aggregate into a community, known as a biofilm, and produce goods to be used by all, and in return, receive protection from external environmental stresses. Biofilms are susceptible to "cheaters" who do not contribute but benefit from the community structure. Biofilms are ubiquitous and are found both in natural environments and in industrial and medical settings, where they can endanger human health and welfare. The goal of this research is to determine whether it is possible for cheater microbes to disrupt and destroy undesirable biofilm communities. Using computer simulations, the research will test whether, and under what conditions, introducing a "Trojan Horse" microbe that produces a lethal toxin could destabilize a biofilm community. The results of the simulations will then be tested using natural and engineered yeast strains. One outcome of this research is that it will provide a proof-of-concept that demonstrates how social evolution theory could be used in important medical and industrial applications where biofilms cause problems. This project will also provide the opportunity for undergraduate and graduate researchers to be trained in an interdisciplinary approach to problem solving? from theory, to simulations, to experiments with living organisms.<br/><br/>Like all cooperative communities, biofilms are susceptible to invasion by selfish individuals who benefit from cooperation, but do not contribute. Therefore, the study of microbial social interactions and their long-term consequences could lead to a better understanding of processes that can destabilize these communities. One such strategy, which would use an engineered "Trojan Horse" strain to infiltrate a biofilm, has been proposed, but not tested with a spatially explicit model or experimental work. In this project researchers will first employ individual-based, spatially explicit, stochastic simulations to model cells interacting a biofilm community. The model will be used to determine how different social strategies influence the growth and distribution of multiple cell types and to investigate how modeled parameters affect the effectiveness of a Trojan Horse strategy to prevent biofilm growth and disrupt an already established community. The second step of the project is to test whether living organisms with the simulated strategies can disrupt biofilms. Natural and engineered strains of the budding yeast Saccharomyces cerevisiae will be utilized. As part of this research, the fitness effects of social phenotypes (biofilm formation and toxin production) will be assessed in a panel of natural yeast strains. The successful completion of this research will contribute to developing a major model organism for social evolutionary studies, as well as explore the possibility of applying social evolution theory to medical and industrial applications.<br/><br/>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.