Phage therapy for the treatment of a virulent Klebsiella pneumoniae infection in a mouse model

Objectives
Klebsiella pneumoniae is an important emerging pathogen in humans and animals with serious clinical consequences. The increased use of antibiotics has promoted the emergence of carbapenem-resistant and β-lactamase (ESBL)-producing K. pneumoniae strains. Recently, phage therapy has gained momentum as a potential alternative against emerging antimicrobial resistance. This study was conducted to evaluate the therapeutic effects of a novel lytic phage (VTCCBPA43) in a pneumonic mouse model to investigate the efficacy of phage therapy against a virulent K. pneumoniae infection.

Methods
The tailed phage VTCCBPA43 was investigated regarding its growth kinetics, its in vitro host range, and its temperature and pH sensitivity. The protein components were analyzed using SDS-PAGE and nLC-MS/MS. Therapeutic efficacy was observed 2 h post-challenge with virulent K. pneumoniae in a BALB/c mouse model.

Results
The phage VTCCBPA43 proved to be highly temperature-tolerant (up to 80°C). It was most active at pH 5, had a burst size of 172 PFU/mL, and exhibited a narrow host range. It was identified as a KP36-like phage through shotgun proteomics. Following intranasal administration of a single dose (2 × 10^9 PFU/mouse) after infection with virulent K. pneumoniae, the presence of a biologically active phage in vivo and a significant reduction in the bacterial load of the lungs were observed at all time points. A reduction in lesion severity indicated an overall positive effect of VTCCBPA43 phage therapy in the pneumonic mouse model.

Translation of the source: https://www.sciencedirect.com/science/article/pii/S2213716519302516?via%3Dihub