Bacteriophages play key roles in bacterial ecology and evolution and are potential antimicrobials. However, the determinants of phage-host specificity remain elusive. Here, we isolate 46 phages to challenge 138 representative clinical isolates of Klebsiella pneumoniae, a widespread opportunistic pathogen. Spot tests show a narrow host range for most phages, with <2% of 6,319 phage-host combinations tested yielding detectable interactions. Bacterial capsule diversity is the main factor restricting phage host range. Consequently, phage-encoded depolymerases are key determinants of host tropism, and depolymerase sequence types are associated with the ability to infect specific capsular types across phage families. However, all phages with a broader host range found do not encode canonical depolymerases, suggesting alternative modes of entry. These findings expand our knowledge of the complex interactions between bacteria and their viruses and point out the feasibility of predicting the first steps of phage infection using bacterial and phage genome sequences.
Klebsiella capsular diversity restricts the host range of most Klebsiella phages
Phage-encoded depolymerase domains can predict capsular tropism
Capsular tropism predictability is limited by post-adsorptive resistance mechanisms
Phages lacking capsule dependency and depolymerases exhibit broader host ranges
Beamud et al. analyze the host tropism of bacteriophages infecting Klebsiella pneumoniae, a nosocomial pathogen of global concern. They identify phage sequence domains that predict capsular tropism, the main determinant of infectivity. This work demonstrates how phenotypic and genomic data can be combined to better understand virus-host interactions.