Project Details
Projekt
Interrogating the contributions of novel immune systems to anti-phage defense in their native bacterial hosts
Applicant
Professor Dr. Chase Beisel
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 465069819
Bacteria and phages have been locked in an evolutionary arms race for billions of years, with phages devising new offensive strategies and bacteria mounting countering defenses. Bacteria were long thought to possess three principal systems that confer antiviral defense: restriction-modification systems, CRISPR-Cas systems, and abortive infection systems. However, recent work has begun to reveal a far larger and more diverse repertoire of defense systems present throughout the bacterial world. Interrogating these systems and their contributions to antiviral defense represents the next major challenge to better understand bacterial-phage interactions and their impact on the environment and our resident microbiomes. To date, the few characterized examples of these novel defense systems involved biochemical studies or heterologous expression in standard laboratory strains. In contrast, defense systems are often integrated within the physiology of their host and co-exist with other present defense systems. What remains unclear is how these defense systems function in their natural context and the level of protection conferred by these systems versus the other resident defenses. Here, we propose to elucidate the antiviral properties of recently discovered defense systems in strains harboring these systems naturally. We have selected Zorya II as a compelling case study, as this system is widely prevalent in bacteria and encodes multiple proteins with unknown functions. Critically, these systems are found in numerous culturable, sequenced, and commercially-available strains of Escherichia coli possessing other defense systems, simplifying the interrogation of Zorya II in its natural context. Our operating hypothesis is that Zorya II elicits cell suicide through chromosomal destruction and provides a non-redundant layer of defense that further protects the bacterial population from phage infection. To test this hypothesis, we will pursue the following two research objectives: Objective 1: Elucidate how Zorya II achieves immune defense. Objective 2: Determine the unique contributions of Zorya II to antiviral defense.These objectives are supported by extensive preliminary data and the PI’s unique expertise in bacterial defense systems, genome editing, and cell-free systems. If successful, the proposed work will provide a mechanistic description of how a novel defense system contributes to antiviral defense in its native host. Such insights would directly support the mission of SPP 2330 by establishing new concepts and mechanisms for antiviral defense in bacteria.
DFG Programme
Priority Programmes
