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Bacterial antiphage defense proteins

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Bacteriophages (phages) are viruses that infect bacteria. They are the most abundant biological entities in the biosphere and coexist with their host. The virus-rich environment and the constant exposure of bacteria to viral infection have led to intense arms-race between bacteria and phages, resulting in the development of diverse and sophisticated antiphage defense systems in bacteria. Bacterial antiviral systems use various phage resistance mechanisms and function during distinct stages of the phage infection cycle. Some of them have been thoroughly characterized for many years, but recently discovered defense systems are poorly characterized. Deciphering their detailed molecular mechanisms will not only contribute to our fundamental understanding of host–parasite interactions in microbiology but also provide useful biotechnological tools such as restriction enzymes and Cas9 nuclease.

 


Among the newly discovered systems, the Thoeris defense system, named after a deity in Egyptian mythology, has been identified in more than 2000 microbial genomes with broad phylogenetic distribution. It was detected in nine different taxonomic phyla, including a wide variety of bacteria and archaea. We reported crystal structures and functional analyses of two protein components (ThsA and ThsB) from the Thoeris defense system. Combined with previous findings, our results are expected to advance the understanding of the molecular mechanism underlying the Thoeris defense system and suggest that NAD+ degradation is a previously unknown strategy for bacterial antiphage resistance.

 

 

Related publication:

1. Oh, H., Koo, J., An, S.Y., Hong, S.H., Suh, J.Y., Bae E.* (2023) "Structural and functional investigation of GajB protein in Gabija anti-phage defense." Nucleic Acids Res 51(21):11941-11951.

2. Ka, D.#, Oh, H.#, Park, E., Kim, J.H. and Bae, E.* (2020) “Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation.” Nat Commun 11(1): 2816.