Abstract
The emergence of multi-drug-resistant bacteria represents a major public-health threat. Phages constitute a promising alternative to chemical antibiotics due to their high host specificity, abundance in nature, and evolvability. However, phage host specificity means that highly diverse bacterial species are particularly difficult to target for phage therapy. This is the case of Klebsiella pneumoniae, which presents a hypervariable extracellular matrix capsule exhibiting dozens of variants. Here, we report four novel phages infecting K. pneumoniae capsular type K22 which were isolated from environmental samples in Valencia, Spain. Full genome sequencing showed that these phages belong to the Podoviridae family and encode putative depolymerases that allow digestion of specific K22 K. pneumoniae capsules. Our results confirm the capsular type-specificity of K. pneumoniae phages, as indicated by their narrow infectivity in a panel of K. pneumoniae clinical isolates. Nonetheless, this work represents a step forward in the characterization of phage diversity, which may culminate in the future use of large panels of phages for typing and/or for combating multi-drug-resistant K. pneumoniae.
Highlights
The emergence of multi-drug-resistant bacterial strains as a result of indiscriminate antibiotic use constitutes a major public-health issue worldwide
Samples were filtered and tested on soft agar semi-solidified media containing a lawn of a clinical isolate (1210) of K. pneumoniae belonging to capsular type K22
Titers after this amplification step ranged from 1 × 1010 to 3 × 1011 plaque forming units (PFU) per mL (Table 1)
Summary
The emergence of multi-drug-resistant bacterial strains as a result of indiscriminate antibiotic use constitutes a major public-health issue worldwide. Phages (viruses that infect bacteria) offer a promising tool to lyse pathogenic bacteria without depleting other species of the microbiome, avoiding dysbiosis Their high specificity poses a difficulty for the development of a curative treatment, since fast bacterial typing (not always feasible) or very large phage panels are needed to combat highly diverse bacteria [1]. For this reason, the use of phage cocktails has been suggested, but this requires a comprehensive analysis of the interactions among cocktail components. Phage cocktails have been already tested in animals and in a few clinical cases, mainly as compassionate treatments, with encouraging results [2]
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