Evolutionary interplay: virulence, endolysin-like hydrolases, and defense correlations in the Erwinia amylovora pangenome.

Erwinia amylovora, the causative agent of fire blight, poses a significant threat to global pome fruit production. This study presents a comprehensive genomic analysis of 317 E. amylovora strains and 227 Erwinia phages to elucidate virulence evolution, phage-host dynamics, and the genomic signatures of the co-evolutionary arms race. Our analysis suggests that a substantial portion of E. amylovora's virulence factors (VFs) share evolutionary origins with diverse plant, human, and animal pathogens, underscoring widespread horizontal gene transfer. We identified bacterial phage hydrolases‑like proteins that share phylogenetic and domain-level similarities with phage endolysins. These observations are consistent with the possibility that some bacterial hydrolases originated from phage-derived ancestors, although functional repurposing remains to be experimentally validated. Crucially, our analysis identifies systematic, non-random associations between bacterial defense systems (e.g., RM, CRISPR-Cas, TA) and mobile anti-defense genes. Statistical correlations show strong patterns of co-occurrence and mutual exclusivity, which are consistent with an ongoing phage-bacteria arms race. These patterns provide a genomic basis for generating hypotheses about co-evolutionary dynamics. These findings may advance our understanding of E. amylovora pathogenicity and phage interactions, offering foundational insights for developing targeted phage-based biocontrol strategies against this devastating plant pathogen. Experimental validation of the predicted virulence factors and defense correlations is warranted to confirm their biological roles.