Li Xiaoyue, Xu Sixiang, Tan Libin, Yan Xiaona, Wang Xin, Li Zhuojun, Chen Long, Zhang Wei
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing, 210095, China; The Sanya Institute of Nanjing Agricultural University, Yabulun Industrial Park, Yazhou Bay Science and Technology City, Sanya, 572024, China.
Department of Clinical Laboratory, Zhangjiagang Hospital Affiliated to Soochow University, Zhangjiagang, 215600, China.
Virology. 2025 Aug;609:110570. doi: 10.1016/j.virol.2025.110570. Epub 2025 May 10.
Urinary tract infections are one of the most common infectious diseases worldwide, with uropathogenic Escherichia coli (UPEC) being the leading cause. Phage therapy has emerged as a promising alternative due to the increasing prevalence of multidrug resistance UPEC strains. In this study, we isolated and characterized a novel phage, vB_EcoP_P64441, which lysed UPEC, including serogroup O75. The phage can survive from 4 to 50 °C and a pH range of 3-11. The optimal MOI was 1, latent period was 4 min, and burst size was 10 PFU/cell. Whole genome sequencing revealed that it consisted of 42,960 base pairs that encoded 53 CDSs, with no lysogenic, toxin, or tRNA-associated genes detected. vB_EcoP_P64441 was classified as a new species within the family Autographiviridae, subfamily Slopekvirinae. The results of the inhibition experiments showed that vB_EcoP_P64441 had a good suppression effect on the growth of planktonic UPEC. Phage either alone or in combination with cefotaxime was effective in inhibiting biofilm formation of UPEC in vitro. Phage strongly inhibited bacterial growth on disposable rubber catheters and limited biofilm formation within 24 h. Cellular infection experiments showed that pretreatment phage could effectively inhibit UPEC adhesion to bladder epithelial cells with safety and reduce the cellular damage caused by UPEC. Our results suggest that vB_EcoP_P64441 is a novel and effective phage for UPEC inhibition with promising applications.
尿路感染是全球最常见的传染病之一，尿路致病性大肠杆菌（UPEC）是主要病因。由于多重耐药UPEC菌株的患病率不断上升，噬菌体疗法已成为一种有前景的替代方法。在本研究中，我们分离并鉴定了一种新型噬菌体vB_EcoP_P64441，它可裂解包括O75血清群在内的UPEC。该噬菌体在4至50°C以及pH值3至11的范围内均可存活。最佳感染复数为1，潜伏期为4分钟，裂解量为10噬菌斑形成单位/细胞。全基因组测序显示，它由42,960个碱基对组成，编码53个编码序列，未检测到溶原性、毒素或与tRNA相关的基因。vB_EcoP_P64441被归类为自养病毒科斜坡病毒亚科内的一个新物种。抑制实验结果表明，vB_EcoP_P64441对浮游UPEC的生长具有良好的抑制作用。噬菌体单独使用或与头孢噻肟联合使用在体外均能有效抑制UPEC生物膜的形成。噬菌体强烈抑制一次性橡胶导管上的细菌生长，并在24小时内限制生物膜的形成。细胞感染实验表明，预处理噬菌体可有效抑制UPEC对膀胱上皮细胞的粘附，并具有安全性，同时减少UPEC引起的细胞损伤。我们的结果表明，vB_EcoP_P64441是一种新型且有效的抑制UPEC的噬菌体，具有广阔的应用前景。
