Genomic evaluation of novel Kenyan virulent phage isolates infecting carbapenemase-producing Klebsiella pneumoniae and safety determination of their lysates in Balb/c mice.

Abstract

This study aimed to evaluate the genomic features of novel Kenyan virulent phage isolates infecting carbapenemase-producing Klebsiella pneumoniae and to determine the safety of their lysates using mice model in a preclinical study. The genomics showed that the Klebsiella phages vB_KpM_CPRSA and vB_KpM_CPRSB belonged to the genus Slopekvirus with a similarity index of less than 92% compared to the most closest relative species. Their genomes did not contain antimicrobial resistance and toxin genes. Then endotoxin levels in the Klebsiella phage lysates were statistically significant (p value ˃ 0.05). The serum activities of aspartate aminotransferase, alanine aminotransferase and urea in the group of balb/c mice injected with bacteriophage lysates through the intravenous route were higher compared to that of the intranasal route. Unexpectedly, there was mild congestion of the central veins of kidneys and liver without damage to renal tubules and hepatocytes and a lack of physical discomfort and pain in the mice. Our study isolated and characterised Klebsiella phages against carbapenem-resistant K. pneumoniae, which are promising therapeutic agents for the treatment of respiratory tract infections using the topical mode of administration as the preferred route of bacteriophage delivery.