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

Autor: Michodigni NF; Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences Technology and Innovation (PAUSTI), Nairobi, Kenya. fmichodign@gmail.com.; Department of Reproductive Health and Biology, Phage Biology Laboratory, Institute of Primate Research (IPR), Nairobi, Kenya. fmichodign@gmail.com., Nyachieo A; Department of Reproductive Health and Biology, Phage Biology Laboratory, Institute of Primate Research (IPR), Nairobi, Kenya., Akhwale JK; Department of Zoology, School of Biological Sciences, Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya., Magoma G; Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences Technology and Innovation (PAUSTI), Nairobi, Kenya.; Department of Biochemistry, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya., Kimang'a AN; Department of Medical Microbiology, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya.
Jazyk: angličtina
Zdroj: Archives of microbiology [Arch Microbiol] 2022 Jul 29; Vol. 204 (8), pp. 532. Date of Electronic Publication: 2022 Jul 29.
DOI: 10.1007/s00203-022-03143-x
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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