The host range of generalist and specialist phages in capsule-diverse Klebsiella hosts is driven by the evolvability of receptor-binding proteins

Capsule diversity is a major limiting factor for phage host range in capsulated bacterial hosts. Phage receptor-binding proteins (RBPs) recognize the capsule and initiate infection, making them key players in phage tropism. In this study, we applied an experimental evolution approach to investigate host range adaptation in a diverse 12-phage community interacting with a Klebsiella spp. community containing 39 distinct capsular types. Our findings revealed that generalist phages possessed highly evolvable RBPs, accumulating non-synonymous mutations that modulated their host range. In contrast, specialist phages acquired fewer mutations but remained stable in the community, maintaining their narrow host range. Additionally, recombination between co-infecting closely related phages facilitated rapid host range adaptation through RBP swapping. However, most recombined genes encoded endonucleases or proteins of unknown function, suggesting their potential role in phage survival. This study advances our understanding of phage host range evolution and provides new insights for optimizing phage-based applications.