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一种靶向与医院感染相关的肺炎克雷伯菌菌株的新型裂解性噬菌体(vB_KpnM_KP1)的特性分析。

Characterization of a new lytic bacteriophage (vB_KpnM_KP1) targeting Klebsiella pneumoniae strains associated with nosocomial infections.

作者信息

Molina-López José, Simon-Olea Berenice, Espinoza-Mellado María Del Rosario, Hernández-Chiñas Ulises, Eslava-Campos Carlos Alberto, Balcázar José Luis, González-Villalobos Edgar

机构信息

Unidad Periférica de Investigación Básica y Clínica en Enfermedades Infecciosas, Departamento de Salud Pública/División de Investigación, Facultad de Medicina, UNAM, C.P. 04510, Mexico City, Mexico; Laboratorio de Patogenicidad Bacteriana, Unidad de Hemato-Oncología e Investigación, Hospital Infantil de México Federico Gómez/Facultad de Medicina UNAM, C.P. 06720, Mexico City, Mexico.

Unidad Periférica de Investigación Básica y Clínica en Enfermedades Infecciosas, Departamento de Salud Pública/División de Investigación, Facultad de Medicina, UNAM, C.P. 04510, Mexico City, Mexico; Laboratorio de Patogenicidad Bacteriana, Unidad de Hemato-Oncología e Investigación, Hospital Infantil de México Federico Gómez/Facultad de Medicina UNAM, C.P. 06720, Mexico City, Mexico; Central de Instrumentación de Microscopía, Depto. Investigación, Instituto Politécnico Nacional-Escuela Nacional de Ciencias Biológicas (IPN-ENCB), Prolongación de Carpio y Plan de Ayala, Mexico City, 11340, Mexico; Laboratorio de Biología Molecular División de Investigación, Departamento de Salud Pública, Facultad de Medicina UNAM, C.P. 04510, Mexico City, Mexico.

出版信息

Virology. 2025 Jun;607:110526. doi: 10.1016/j.virol.2025.110526. Epub 2025 Apr 4.

Abstract

A new bacteriophage, vB_KpnM_KP1, was identified and characterized, exhibiting a strong lytic effect on Klebsiella pneumoniae. Host range analysis revealed its effectiveness against 77.4% of clinical strains, achieving complete lysis of those associated with urinary tract infections (UTIs). Phage stability tests demonstrated that vB_KpnM_KP1 remained stable at neutral pH and across all tested temperatures. However, inactivation was observed at high ethanol concentrations and extreme pH levels. Transmission electron microscopy (TEM) analysis identified vB_KpnM_KP1 as a Myo-type phage with an icosahedral head and a contractile tail. Moreover, genome annotation of vB_KpnM_KP1 revealed a linear DNA genome of 174,802 bp, containing 307 open reading frames. Functional predictions suggest the presence of genes involved in DNA replication, transcription, morphogenesis, and cell lysis. Phylogenetic analysis classified vB_KpnM_KP1 within the Slopekvirus genus of the Straboviridae family, showing high sequence identity with phages that infect Enterobacter, Escherichia and Klebsiella species. These findings highlight the potential of phage vB_KpnM_KP1 as an alternative treatment for multidrug-resistant K. pneumoniae infections, particularly in UTIs, while offering valuable insights into its stability and genetic composition.

摘要

一种新的噬菌体vB_KpnM_KP1被鉴定并表征,它对肺炎克雷伯菌表现出强烈的裂解作用。宿主范围分析表明,它对77.4%的临床菌株有效,能完全裂解与尿路感染(UTIs)相关的菌株。噬菌体稳定性测试表明,vB_KpnM_KP1在中性pH值和所有测试温度下都保持稳定。然而,在高乙醇浓度和极端pH值水平下观察到其失活。透射电子显微镜(TEM)分析确定vB_KpnM_KP1为肌尾型噬菌体,具有二十面体头部和收缩性尾部。此外,vB_KpnM_KP1的基因组注释显示其线性DNA基因组为174,802 bp,包含307个开放阅读框。功能预测表明存在参与DNA复制、转录、形态发生和细胞裂解的基因。系统发育分析将vB_KpnM_KP1归类于Straboviridae科的Slopekvirus属,与感染肠杆菌、大肠杆菌和克雷伯菌属的噬菌体具有高度序列同一性。这些发现突出了噬菌体vB_KpnM_KP1作为多重耐药肺炎克雷伯菌感染,特别是尿路感染的替代治疗方法的潜力,同时为其稳定性和遗传组成提供了有价值的见解。

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