# Therapeutic efficacy of a K5-specific phage and depolymerase against Klebsiella pneumoniae in a mouse model of infection

## TL;DR

Researchers tested a phage and its enzyme against a drug-resistant Klebsiella strain in mice, finding the enzyme more effective at treating infections.

## Contribution

A K5-specific phage and its depolymerase were characterized and shown to effectively treat K. pneumoniae in a mouse model.

## Key findings

- Phage P1011 achieved 60% survival in mice with phage-supporting bacteria and reduced bacterial load in organs.
- Phage therapy also reduced viable bacteria in mice with phage-resistant bacteria.
- Depolymerase dep1011 achieved 100% survival in both phage-compatible and incompatible bacterial models.

## Abstract

Klebsiella pneumoniae has become one of the most intractable gram-negative pathogens infecting humans and animals due to its severe antibiotic resistance. Bacteriophages and protein products derived from them are receiving increasing amounts of attention as potential alternatives to antibiotics. In this study, we isolated and investigated the characteristics of a new lytic phage, P1011, which lyses K5 K. pneumoniae specifically among 26 serotypes. The K5-specific capsular polysaccharide-degrading depolymerase dep1011 was identified and expressed. By establishing murine infection models using bovine strain B16 (capable of supporting phage proliferation) and human strain KP181 (incapable of sustaining phage expansion), we explored the safety and efficacy of phage and dep1011 treatments against K5 K. pneumoniae. Phage P1011 resulted in a 60% survival rate of the mice challenged with K. pneumoniae supporting phage multiplication, concurrently lowering the bacterial burden in their blood, liver, and lungs. Unexpectedly, even when confronted with bacteria impervious to phage multiplication, phage therapy markedly decreased the number of viable organisms. The protective efficacy of the depolymerase was significantly better than that of the phage. The depolymerase achieved 100% survival in both treatment groups regardless of phage propagation compatibility. These findings indicated that P1011 and dep1011 might be used as potential antibacterial agents to control K5 K. pneumoniae infection.