Understanding the nature of anti-phage defense islands in microbes

• Applicant: Professor Dr. 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

Bacteria are engaged in a continuous arms race in which they seek to defend themselves against rapidly evolving phages. To this end, bacteria evolved dedicated defense systems, including restriction-modification, CRISPR-Cas, abortive infection, and a large diversity of additional defense systems. Analysis of bacterial and archaeal genomes have shown that defense systems are non-randomly distributed in microbial genomes, and are clustered to specific genomic locations that were termed “defense islands”. This property of defense systems allowed the prediction, and later the experimental verification, of numerous novel anti-phage defense systems based on their preferential genomic localization near restriction systems, CRISPR-Cas, and other known defense systems in multiple microbial genomes. Although the concept of defense islands have been instrumental for the recent discovery of many defense systems, the nature of defense islands themselves remained vague. What are defense islands? What defines a defense island? Are defense islands involved in transferring defense systems between microbial genomes? If so, how? How often do they appear in microbial genomes? These questions are currently completely unanswered and will be addressed in the current proposed project. As part of our preliminary, unpublished results, we developed methodologies that allow to identify the exact boundaries of defense islands within the microbial genome. With these data, we found preliminary evidence suggesting that some defense islands are mobile genetic elements dedicated for carrying and mobilizing defense systems between genomes. In the current proposal we present a combined computational/experimental plan to comprehensively map defense islands in a large set of microbial genomes, understand their content, integration patterns, and mobility between genomes. This will allow us to understand how defense islands spread phage resistance traits between genomes, 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