Prophages express a type IV pilus component to provide anti-phage defence

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Abstract

Phage genomes integrated within bacterial genomes, known as prophages, frequently encode proteins that provide defence against further phage infection. These proteins often function at the cell surface and prevent phages from attaching to their host receptor. Here, we describe the discovery of prophage-encoded proteins that resemble FimU, a component of the Pseudomonas aeruginosa type IV pilus. These phage FimU proteins are incorporated into the pilus without altering its function, yet they mediate robust protection against infection by phages that bind to the tip of the pilus, where FimU is likely located. The phage FimU proteins and the phage tail proteins that interact with FimU are highly diverse, suggesting that evolution in this system is driven by phage versus phage competition. To our knowledge, this is the first example of anti-phage defence mediated by replacement of a bacterial cell surface component with a phage-encoded protein.

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  1. Overall, it appears that the F10-like phage precursors may have gained an initial evolutionary advantage by targeting FimU, which is not targeted by other phages.

    Do you have any speculative thoughts on whether this strategy could also have a secondary impact on other aspects of PAO fitness? i.e. PAO–eukaryotic host interactions, surface composition in general, other T4 functions

  2. expression of the different P-FimU proteins had variable effects on the F10-like phages tested

    Super interesting! Do you think this is rooted in variable binding affinities? Would be cool if that matters for biological outcomes here. And if you could predict that somehow.

  3. We found that each of these structures overlaid well with the solved structure of Pae strain PAO1 FimU with root mean square deviations in structure ranging from 2.4 to 3.0 over at least 130 backbone positions (Extended Data Fig. 1b)

    In light of this, curious if you've done or are planning to do any predicted-structure-based searches as well, in addition to BLAST. Would be interesting to see if you pull out anything interesting using that search?

    If it's helpful, our protein cartography tool could possibly help with some of this workflow. And I'm kind of curious whether there are any hits outside of phage. Such as other endosymbionts of bacteria or even hosts that might also use this strategy to regulate phage/bacteria interactions.