Capsid redirection mechanism of the Staphylococcus aureus pathogenicity island SaPIpT1028

Staphylococcus aureus pathogenicity islands (SaPIs) are prototypical members of the phage-inducible chromosomal islands (PICI) family. These elements redirect helper phage capsid assembly to produce smaller capsids, accommodating the satellite genome while excluding the phage genome. This study identifies how SaPIpT1028 mediates capsid redirection through a unique gene, rcm (redirecting capsid morphogenesis). While rcm has no sequence similarity to known capsid assembly regulators, our results demonstrate that its expression is necessary and sufficient for redirecting capsid morphogenesis in S. aureus phages, such as φ7206. We show that, to do this, Rcm interacts with the φ7206 major capsid protein. Comparative evolutionary and structural analyses reveal functional parallels between Rcm and CpmB, a regulator used by other SaPIs. However, Rcm has evolved a multi-helical topology to match the multi-helical topology of the scaffold protein of φ7206. Sequence homology and AlphaFold predictions suggest that Rcm competitively interacts with the φ7206 scaffold protein, altering capsid size through a mechanism akin to CpmB. This work highlights SaPI adaptation, exemplified by Rcm's ability to exploit phages resistant to other remodellers, while inhibiting their reproduction. These findings underscore the dynamic co-evolution of phages and SaPIs, with Rcm playing a pivotal role in capsid size regulation and phage interference.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.