Understanding the nature of anti-phage defense islands in microbes

• Applicant: Professor Rotem Sorek, Ph.D.
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; General Genetics and Functional Genome Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 464312965

Over 150 different types of anti-phage defense systems were reported to date, most of which were discovered recently. The recent revolution in our understanding of defense systems was driven by the realization that bacterial defense systems are frequently clustered in specific genomic locations called “defense islands”. This property of defense systems allowed the discovery of numerous novel anti-phage defense systems based on their preferential genomic localization within defense islands in multiple microbial genomes. The purpose of the current project is to understand what defense islands are, how they are distributed across microbial genomes, and how they contribute to dissemination of defense systems through horizontal gene transfer. During the first term of the project, we developed methodologies to identify the exact boundaries of defense islands within microbial genomes. With this method at hand, we analyzed over 1000 E. coli genomes and found that defense islands in E. coli are usually carried on mobile genetic elements that preferentially integrate at several dozens of dedicated hotspots in the E. coli genome. Our data show that the overwhelming majority of the E. coli pan-immune system is on defense islands carried by mobile genetic elements (Hochhauser et al, PLoS Genetics 2023). In the second term of the project we will expand defense islands analysis to ~50,000 genomes widely spread across the phylogenetic tree of bacteria. Accurate determination of island boundaries will allow us to understand commonalities and differences in defense system dissemination strategies among different types of bacteria, and furthermore to discover new families of anti-phage defense systems that so far escaped detection.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2330: New concepts in prokaryotic virus-host interactions - from single cells to microbial communities
• International Connection: Israel