Abstract
Klebsiella pneumoniae carries a thick polysaccharide capsule. This highly variable chemical structure plays an important role in its virulence. Many Klebsiella bacteriophages recognize this capsule with a receptor binding protein (RBP) that contains a depolymerase domain. This domain degrades the capsule to initiate phage infection. RBPs are highly specific and thus largely determine the host spectrum of the phage. A majority of known Klebsiella phages have only one or two RBPs, but phages with up to 11 RBPs with depolymerase activity and a broad host spectrum have been identified. A detailed bioinformatic analysis shows that similar RBP domains repeatedly occur in K. pneumoniae phages with structural RBP domains for attachment of an RBP to the phage tail (anchor domain) or for branching of RBPs (T4gp10-like domain). Structural domains determining the RBP architecture are located at the N-terminus, while the depolymerase is located in the center of protein. Occasionally, the RBP is complemented with an autocleavable chaperone domain at the distal end serving for folding and multimerization. The enzymatic domain is subjected to an intense horizontal transfer to rapidly shift the phage host spectrum without affecting the RBP architecture. These analyses allowed to model a set of conserved RBP architectures, indicating evolutionary linkages.
Highlights
Closely related phages are characterized by a synteny of conserved structural genes interrupted by divergent receptor binding protein (RBP) genes, which are subject to intensive horizontal transfer
We inspected the region of structural genes across different Klebsiella phages within specific phage genera to identify potential RBPs based on a broken synteny
We analyzed the presence of putative enzymatic domains within the identified RBPs
Summary
Since 2013 K. pneumoniae has been marked as a prominent member of the carbapenem-resistant Enterobacteriaceae (CRE), featured by a multidrug-resistant phenotype and labeled as a class of antibiotic-resistant bacteria for which novel ways of therapy are most urgent (Weiner et al, 2016; Calfee, 2017). Bacteriophages have since long been proposed as promising alternatives to antibiotic therapy. The large majority of phages is highly specific with a host spectrum defined at the species/strain level. This high specificity necessitates the selection of a phage sur-mesure for a personalized treatment or the use of a phage cocktail that covers a broader host range.
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