Genomic Characterization and Therapeutic Potential of the Lytic Bacteriophage Curly against Klebsiella pneumoniae in Human Innate Immune Cells and a Murine Pneumonia Model

Klebsiella pneumoniae is a major cause of severe respiratory and systemic infections, and the rise of multidrug-resistant strains has driven the need for new antibacterial approaches. To address this issue, researchers studied nine K. pneumoniae-infecting bacteriophages, isolates from various environmental sources. Analyzing their genomes and proteins, they found that Curly showed the strongest potential as an antibacterial agent.

Curly was highly effective in suppressing bacterial growth in liquid culture and reduced the bacterial load in both cell-associated and cell-free fractions within primary human immune cell cultures. Transmission electron microscopy revealed phage-like particles within bacterial profiles in both extracellular and intracellular compartments of macrophages.

In a mouse pneumonia model, intranasal administration of Curly reduced pulmonary bacterial burden in a dose-dependent manner, with significant reductions at both low and high doses. Additionally, Curly treatment decreased lung inflammation and preserved lung structure, demonstrating its potential as a therapeutic phage candidate against K. pneumoniae.