Bacteriophages (phages) are viral parasites that infect bacteria. The increasing prevalence of antimicrobial resistance (AMR) has resulted in greater interest in phages as potential therapeutics. Unfortunately, phages often possess incredibly limited host ranges and phage resistant bacteria evolve rapidly both in vitro and in vivo, which has limited the effectiveness of phage-based therapies.
To gain a greater understanding into the lifecycle of phages infecting the clinically relevant Klebsiella genus, we isolated two closely related phages (DAS1 and DAS2) that infected an environmental Klebsiella oxytoca strain. Unlike previously characterised Klebsiella targeting phages, these phages possessed a broad host range that extended across multiple distinct Klebsiella species (including clinical isolates of Klebsiella pneumoniae) and also included members of the closely related Raoultella genus. Despite sharing 98% sequence homology these two phages possess distinct tail fibre proteins which likely contributes to their slightly different host ranges.
Genome sequencing of phage resistant mutants revealed that mutations in genes involved in synthesis of the LPS core of host bacteria resulted in resistance to phage infection. In addition to mutations in single genes, one phage resistant mutant possessed a deletion of over 170kb resulting in the loss of key virulence factors and demonstrating the extreme adaptions that can be selected for by phage predation. Further characterising the mechanisms that facilitate the broad host ranges of these phages may help provide insight into the complex interactions between phage and host and potentially aid in the development of broader range phage treatments.