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.
摘要：
本研究旨在评估感染产生碳青霉烯酶的肺炎克雷伯菌的新型肯尼亚毒力噬菌体分离株的基因组特征，并在临床前研究中使用小鼠模型确定其裂解物的安全性。基因组学表明，克雷伯菌噬菌体vB_KpM_CPRSA和vB_KpM_CPRSB属于Slopekvirus属，与最接近的近缘种相比，相似性指数小于92％。他们的基因组不包含抗微生物药物抗性和毒素基因。然后，克雷伯氏菌噬菌体裂解物中的内毒素水平具有统计学意义（p值0.05）。天冬氨酸转氨酶的血清活性，与鼻内途径相比，通过静脉途径注射噬菌体裂解物的balb/c小鼠组的丙氨酸氨基转移酶和尿素更高。出乎意料的是,小鼠肾脏和肝脏的中央静脉轻度充血，而肾小管和肝细胞没有损伤，也没有身体不适和疼痛。我们的研究分离并鉴定了针对耐碳青霉烯的肺炎克雷伯菌噬菌体，它们是使用局部给药模式作为噬菌体递送的优选途径来治疗呼吸道感染的有前途的治疗剂。
