Structural Determinants of SlpA-Mediated Phage Recognition in Clostridioides difficile

Phage therapy is a promising approach, but its clinical application against C. difficile remains hindered by our lack of understanding of the factors driving host specificity. Indeed, it is crucial to understand how phages specifically interact with their host to be able to select the best candidates for cocktail preparation.

The main surface layer protein SlpA is a key phage receptor, but the molecular details governing phage-receptor interactions remain unclear. By dissecting the structural features of SlpA required for phage infection through engineered isoforms and domain modifications, we reveal how specific regions of SlpA mediate phage adsorption and infection. These new insights into phage–receptor interactions will be instrumental in guiding the future engineering of broad-host-range therapeutic phages.