Hussein Assmaa H, Makky Salsabil, Hager Raghda, Connerton Ian F, El-Shibiny Ayman
Center for Microbiology and Phage Therapy, Zewail City of Science and Technology, Giza, 12578, Egypt.
Basic Medical Science Department, Faculty of Medicine, King Salman International University, Eltor, South Sinai, Egypt.
BMC Microbiol. 2025 Apr 16;25(1):221. doi: 10.1186/s12866-025-03903-x.
Urinary tract infections (UTIs) caused by antibiotic-resistant bacteria have become a significant public health concern. The increasing ineffectiveness of antibiotics has led to a renewed focus on investigating other strategies, such as bacteriophages, to target specific pathogenic bacteria and prevent future resistance.
This study reports the isolation and characterization of bacteriophage vB_Eco_ZCEC08 targeting uropathogenic Escherichia coli (UPEC). Phage vB_Eco_ZCEC08 is morphologically a non-contractile tailed phage that exhibits strong lytic activity against UPEC with a short latent period of less than 15 min and a lysis time of 20 min to produce a high burst of around 900 phage particles per host cell. vB_Eco_ZCEC08 phage activity demonstrated exceptional stability against temperature [-80-60 ̊C], pH [2-11], UV exposure and incubation in artificial human urine. The phage effectively reduced UPEC counts over a range of infection rates, with MOI 1 the most effective, and which resulted in the limited emergence of phage-insensitive bacteria. A whole-genome study of the 47.926 bp vB_Eco_ZCEC08 phage identified one tRNA gene and 84 predicted genes. Comparative genomics and phylogenetic analysis suggest that the vB_Eco_ZCEC08 phage belongs to the same genus as the Salmonella phage vB_SenS_ST1 but represents a new species. Phage vB_Eco_ZCEC08 showed minimal cytotoxicity against human urinary bladder cancer and skin fibroblast cell lines.
vB_Eco_ZCEC08 phage demonstrates strong selective lytic activity against UPEC in the absence of any lysogenic behavior. These properties coupled with inherent physiochemical stability and low cytotoxicity support the development of vB_Eco_ZCEC08 as an alternative treatment for multidrug-resistant UPEC.
由抗生素耐药菌引起的尿路感染（UTIs）已成为一个重大的公共卫生问题。抗生素有效性的不断降低促使人们重新关注研究其他策略，如噬菌体，以靶向特定病原菌并防止未来出现耐药性。
本研究报告了靶向尿路致病性大肠杆菌（UPEC）的噬菌体vB_Eco_ZCEC08的分离与特性。噬菌体vB_Eco_ZCEC08在形态上是一种非收缩性尾噬菌体，对UPEC表现出强烈的裂解活性，潜伏期短于15分钟，裂解时间为20分钟，每个宿主细胞可产生约900个噬菌体颗粒的高爆发量。vB_Eco_ZCEC08噬菌体活性在温度[-80 - 60℃]、pH值[2 - 11]、紫外线照射以及在人工人尿中孵育的情况下表现出非凡的稳定性。该噬菌体在一系列感染率范围内有效降低了UPEC数量，其中感染复数（MOI）为1时最为有效，且导致噬菌体不敏感细菌的出现有限。对47926 bp的vB_Eco_ZCEC08噬菌体进行的全基因组研究鉴定出一个tRNA基因和84个预测基因。比较基因组学和系统发育分析表明，vB_Eco_ZCEC08噬菌体与沙门氏菌噬菌体vB_SenS_ST1属于同一属，但代表一个新物种。噬菌体vB_Eco_ZCEC08对人膀胱癌和皮肤成纤维细胞系显示出最小的细胞毒性。
vB_Eco_ZCEC08噬菌体在不存在任何溶原性行为的情况下，对UPEC表现出强大的选择性裂解活性。这些特性加上固有的物理化学稳定性和低细胞毒性，支持将vB_Eco_ZCEC08开发为多重耐药UPEC的替代治疗方法。
