Bacterial anti-phage systems are frequently clustered in microbial genomes, forming defense islands. This property enabled the recent discovery of multiple defense systems based on their genomic co-localization with known systems, but the full arsenal of anti-phage mechanisms remains unknown. We report the discovery of 21 defense systems that protect bacteria from phages, based on computational genomic analyses and phage-infection experiments. We identified multiple systems with domains involved in eukaryotic antiviral immunity, including those homologous to the ubiquitin-like ISG15 protein, dynamin-like domains, and SEFIR domains, and show their participation in bacterial defenses. Additional systems include domains predicted to manipulate DNA and RNA molecules, alongside toxin-antitoxin systems shown here to function in anti-phage defense. These systems are widely distributed in microbial genomes, and in some bacteria, they form a considerable fraction of the immune arsenal. Our data substantially expand the inventory of defense systems utilized by bacteria to counteract phage infection.
Shango is a three genes defense system which was discovered in parallel in two works in both *E.coli* and *P.aeruginosa* and was shown to have antiphage activity against the Lambda-phage in *E.coli*[1] and against diverse podo- and siphoviridae in *P.aeruginosa*[2].
Shango is a three genes defense system which was discovered in parallel in two works in both *E.coli* and *P.aeruginosa* and was shown to have antiphage activity against the Lambda-phage in *E.coli*:ref{doi=10.1016/j.chom.2022.09.017} and against diverse podo- and siphoviridae in *P.aeruginosa*:ref{doi=10.1093/nar/gkad317}.
Shango is composed of (i) a TerB-like domain, (ii) an Helicase and (iii) an ATPase. The TerB domain was previously shown to be associated to the perisplasmic membrane of bacteria [3].
Shango is composed of (i) a TerB-like domain, (ii) an Helicase and (iii) an ATPase. The TerB domain was previously shown to be associated to the perisplasmic membrane of bacteria :ref{doi=10.4149/gpb_2011_03_286}.
## Molecular mechanism
The exact mechanism of action of the Shango defense has not yet been characterized, but it was shown that the TerB domain and the catalytic activity of the ATPase and the Helicase are required to provide antiviral defense. The fact that TerB domains are known to be associated to the periplasmic membrane could indicate that Shango might be involved in membrane surveillance [1].
The exact mechanism of action of the Shango defense has not yet been characterized, but it was shown that the TerB domain and the catalytic activity of the ATPase and the Helicase are required to provide antiviral defense. The fact that TerB domains are known to be associated to the periplasmic membrane could indicate that Shango might be involved in membrane surveillance :ref{doi=10.1016/j.chom.2022.09.017}.
Shango was discovered in parallel by Adi Millman (Sorek group) and the team of J. Bondy-Denomy (UCSF).
[1] Millman, A., Melamed, S., Leavitt, A., Doron, S., Bernheim, A., Hör, J., Garb, J., Bechon, N., Brandis, A., Lopatina, A., Ofir, G., Hochhauser, D., Stokar-Avihail, A., Tal, N., Sharir, S., Voichek, M., Erez, Z., Ferrer, J. L. M., Dar, D., … Sorek, R. (2022). An expanded arsenal of immune systems that protect bacteria from phages. _Cell Host & Microbe_, _30_(11), 1556-1569.e5. [https://doi.org/10.1016/j.chom.2022.09.017](https://doi.org/10.1016/j.chom.2022.09.017)
[2] Johnson, Matthew, Laderman, Eric, Huiting, Erin, Zhang, Charles, Davidson, Alan, & Bondy-Denomy, Joseph. (2022). _Core Defense Hotspots within Pseudomonas aeruginosa are a consistent and rich source of anti-phage defense systems_. [https://doi.org/10.5281/ZENODO.7254690](https://doi.org/10.5281/ZENODO.7254690)
[3] Alekhina, O., Valkovicova, L., & Turna, J. (2011). Study of membrane attachment and in vivo co-localization of TerB protein from uropathogenic Escherichia coli KL53. _General physiology and biophysics_, _30_(3), 286-292.
