Structural Determinants of SlpA-Mediated Phage Recognition in Clostridioides difficile

The emergence of Clostridioides difficile as a leading cause of healthcare-associated nosocomial intestinal infections calls for novel therapeutic strategies, particularly in the context of antibiotic resistance and recurrent disease. 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. This dataset comprises genome sequences of the wiltdype R20291 strain, as well as two mutants derived from this strain. One is the FM2.5 slpA null mutant, carying a point mutation in the slpA gene causing a severe truncation of the protein and the absence of an S-layer at the surface of the cell. The other mutant is a newly created deletion mutant in wich the complete slpA gene was removed using CRISPR-Cas. The 3 strains have been resequenced by Oxford Nanopore long read, and Aviti short reads.