Structural Basis for Salmonella Infection by Two Novel Microviridae Phages

Abstract The global resurgence of multidrug-resistant Salmonella species, responsible for millions of annual infections, underscores the urgent need for alternative antimicrobial strategies, such as phage therapy. Microviridae phages offer the promising model for studying phage-host interactions with their unique structural and infection mechanisms. Here, we present the cryo-EM structures of two novel Bullavirinae phages, PJNS001 and PJNS002 at the resolution of 2.68 Å and 2.59 Å, respectively. These icosahedral capsids with T=1 symmetry exhibit a unique vertex reinforcement mechanism, stabilizing the viral assembly. The phage-host engagement is decoded through structural analysis and binding determination. Meanwhile, the intermediate attachment stages captured in situ provide insights into host specificity and infection transitions. These findings not only elucidate the structural basis of phage infection targeting Salmonella, but also establish a paradigm shift in phage engineering, paving the way for next-generation antibacterial development.