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Viral infection

A never-ending defence fight

Nature Reviews Microbiology volume 22, page 62 (2024)Cite this article

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Bacteria and the viruses that infect them, known as bacteriophages (phages), are in a constant evolutionary arms race in which both microorganisms adapt and evolve defence and evasion mechanisms against each other. Until a few years ago, bacterial immunity against phages was considered to comprise mainly of CRISPR–Cas and restriction–modification systems, but recent studies have shown that bacteria encode more than a hundred kinds of defence systems. How these defence systems protect against phages and how phages may have evolved to evade host immunity remain unknown.

In a separate but related study, Antine et al. build on these findings to explain the mechanism of how Gabija defends against phage infection and how the phage Gad1 protein enables immune evasion. Notably, Gabija is one of the most abundant defence systems occurring in over 15% of all bacteria and archaea. The Gabija system is composed of Gabija protein A (GajA) and Gabija protein B (GajB), which together protect cells against diverse phages. Antine et al. combined X-ray crystallography and cryo-electron microscopy and discovered that GajA adopts a tetrameric conformation and acts as a DNA endonuclease, whereas GajB forms two sets of dimers that locate to opposite sides of the GajA tetramer, constituting the Gabija complex (GajAB). The authors introduced mutations in the GajA–GajB oligomerization interface, as well as in the GajA–GajA and GajB–GajB interfaces, and demonstrated that the formation of GajAB is necessary for anti-phage defence activity. The authors further show that phage Gad1 directly binds to the GajAB complex to inactivate host immunity. Upon GajAB recognition, Gad1 assembles into an octamer that binds to the GajAB complex and inhibits phage DNA recognition and cleavage, thus completely abolishing Gabija defence.

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  1. Nature Reviews Microbiology http://www.nature.com/nrmicro/

    Agustina Taglialegna

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  1. Agustina Taglialegna
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Correspondence to Agustina Taglialegna.

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Taglialegna, A. A never-ending defence fight. Nat Rev Microbiol 22, 62 (2024). https://doi.org/10.1038/s41579-023-01006-w

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