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新型裂解噬菌体 vB_EcoS_UTEC10 对具有强大生物膜清除活性的多重耐药大肠杆菌的体外和体内评估。

In vitro and in vivo assessment of the competence of a novel lytic phage vB_EcoS_UTEC10 targeting multidrug resistant Escherichia coli with a robust biofilm eradication activity.

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.

Department of Physiology, College of Medicine, Northern Border University, Arar, Saudi Arabia; Department of Physiology, College of Medicine, Zagazig University, Egypt.

出版信息

Microb Pathog. 2024 Dec;197:107058. doi: 10.1016/j.micpath.2024.107058. Epub 2024 Oct 23.

DOI:10.1016/j.micpath.2024.107058
PMID:39447656
Abstract

Escherichia coli (E. coli) is a leading cause of human infections worldwide and is considered a major cause of nosocomial infections, sepsis, meningitis and diarrhea. Lately, there has been an alarming increase in the incidence of antimicrobial resistance among clinical E. coli isolates. In the current study, a novel bacteriophage (phage) vB_EcoS_UTEC10 was isolated and characterized. The isolated phage showed high stability over wide temperature and pH ranges beside its promising bacteriolytic activity against multidrug resistant (MDR) E. coli isolates. In addition, vB_EcoS_UTEC10 showed a marked antibiofilm capability against mature E. coli biofilms. Genomic investigation revealed that vB_EcoS_UTEC10 has a double stranded DNA genome that consists of 44,772 bp comprising a total of 73 open reading frames (ORFs), out of which 35 ORFs were annotated as structural or functional proteins, and none were related to antimicrobial resistance or lysogeny. In vivo investigations revealed a promising bacteriolytic activity of vB_EcoS_UTEC10 against MDR E. coli which was further supported by a significant reduction in bacterial load in specimens collected from the phage-treated mice. Histopathology examination demonstrated minimal signs of inflammation and necrosis in the tissues of phage-treated mice compared to the degenerative tissue damage observed in untreated mice. In summary, the present findings suggest that vB_EcoS_UTEC10 has a remarkable ability to eradicate MDR E. coli infections and biofilms. These findings could be further invested for the development of targeted phage therapies that offer a viable alternative to traditional antibiotics against resistant E. coli.

摘要

大肠杆菌(E. coli)是全球人类感染的主要原因,被认为是医院感染、败血症、脑膜炎和腹泻的主要原因。最近,临床大肠杆菌分离株对抗菌药物的耐药性发生率令人震惊地增加。在目前的研究中,分离和鉴定了一种新型噬菌体(噬菌体)vB_EcoS_UTEC10。该分离的噬菌体在广泛的温度和 pH 范围内表现出很高的稳定性,除了对多药耐药(MDR)大肠杆菌分离株具有有前途的溶菌活性外。此外,vB_EcoS_UTEC10 对成熟的大肠杆菌生物膜表现出显著的抗生物膜能力。基因组调查显示,vB_EcoS_UTEC10 具有双链 DNA 基因组,由 44,772 bp 组成,总共包含 73 个开放阅读框(ORFs),其中 35 个 ORFs 被注释为结构或功能蛋白,没有一个与抗菌药物耐药性或溶原性有关。体内研究表明,vB_EcoS_UTEC10 对 MDR 大肠杆菌具有有前途的溶菌活性,这一结果得到了从噬菌体处理的小鼠中收集的标本中细菌负荷显著降低的支持。组织病理学检查显示,与未治疗的小鼠观察到的退行性组织损伤相比,噬菌体处理的小鼠组织中的炎症和坏死迹象最小。总之,目前的研究结果表明,vB_EcoS_UTEC10 具有显著消除 MDR 大肠杆菌感染和生物膜的能力。这些发现可以进一步投资于靶向噬菌体治疗的开发,为对抗耐药大肠杆菌提供一种可行的传统抗生素替代方案。

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