CAREER: Uncovering natural metabolite influences on anti-bacteriophage defenses

Indiana University, Bloomington IN

Investigators

Abstract

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). Bacteria can get “sick” too; they can be infected by bacteriophage viruses (or “phages”). The world needs to care about the health of bacteria because many bacteria help humans (food production, medicine production, probiotics), and some bacteria hurt humans (infect humans, destroy food, contaminate industrial processes). Therefore, viruses that infect beneficial bacteria can be problematic, but viruses that infect harmful bacteria actually can help humans. The proposed research program will uncover conditions that help bacteria evade infections by phages. The findings will reveal approaches to protect beneficial bacteria and to leverage viruses to kill harmful bacteria. The research team will be composed of undergraduate students and graduate students and its success will be evaluated. Bacteria have evolved myriad immune systems to protect themselves from viruses (bacteriophages). However, it is unclear how these immune defenses are influenced by local environments. For example, bacteria frequently are found in polymicrobial communities. While there, bacteria are bombarded by a metabolites secreted by their neighbors. These metabolites are likely to influence the efficacy of the antiviral immune systems of the bacteria. Therefore, it is unclear how significant anti-phage defenses are at providing immunity within complex microbiomes. The proposed work will advance knowledge to fill this gap. Specifically, the research team will 1) identify the specific pure metabolites that modulate each of five different antiviral defenses, 2) elucidate the mechanisms by which the metabolites elicit their effects, and 3) determine the prevalence of these metabolite/immunity interactions in host-associated and environmental niches. By characterizing metabolites that modulate antiviral defenses, this research will define specific biochemical environments in which anti-phage defenses provide altered immunity. The community can then leverage metagenomic data to determine the likelihood of the anti-phage defenses to co-occur with these metabolites that modulate them. Furthermore, many antiviral immune systems are incompletely understood. By uncovering the mechanisms of action of the first chemical modulators of these defenses, this project will reveal new details about how these defenses confer immunity. 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.