Feng Tingting, Leptihn Sebastian, Dong Ke, Loh Belinda, Zhang Yan, Stefan Melanie I, Li Mingyue, Guo Xiaokui, Cui Zelin
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhejiang University-University of Edinburgh Institute (ZJU-UoE), Zhejiang University, Haining, China.
Front Microbiol. 2021 Apr 22;12:602902. doi: 10.3389/fmicb.2021.602902. eCollection 2021.
Phage therapy represents a possible treatment option to cure infections caused by multidrug-resistant bacteria, including methicillin and vancomycin-resistant , to which most antibiotics have become ineffective. In the present study, we report the isolation and complete characterization of a novel phage named JD219 exhibiting a broad host range able to infect 61 of 138 clinical strains of tested, which included MRSA strains as well. The phage JD419 exhibits a unique morphology with an elongated capsid and a flexible tail. To evaluate the potential of JD419 to be used as a therapeutic phage, we tested the ability of the phage particles to remain infectious after treatment exceeding physiological pH or temperature. The activity was retained at pH values of 6.0-8.0 and below 50°C. As phages can contain virulence genes, JD419's complete genome was sequenced. The 45509 bp genome is predicted to contain 65 ORFs, none of which show homology to any known virulence or antibiotic resistance genes. Genome analysis indicates that JD419 is a temperate phage, despite observing rapid replication and lysis of host strains. Following the recent advances in synthetic biology, JD419 can be modified by gene engineering to remove prophage-related genes, preventing potential lysogeny, in order to be deployed as a therapeutic phage.
噬菌体疗法是治疗由多重耐药细菌引起的感染的一种可能的治疗选择,这些细菌包括耐甲氧西林和耐万古霉素的细菌,大多数抗生素对它们已经无效。在本研究中,我们报告了一种名为JD219的新型噬菌体的分离和完整表征,该噬菌体具有广泛的宿主范围,能够感染所测试的138株临床菌株中的61株,其中包括耐甲氧西林金黄色葡萄球菌(MRSA)菌株。噬菌体JD419呈现出独特的形态,具有细长的衣壳和灵活的尾部。为了评估JD419作为治疗性噬菌体的潜力,我们测试了噬菌体颗粒在超过生理pH值或温度处理后仍保持感染性的能力。在pH值为6.0 - 8.0且低于50°C时,其活性得以保留。由于噬菌体可能含有毒力基因,我们对JD419的完整基因组进行了测序。45509 bp的基因组预计包含65个开放阅读框(ORF),其中没有一个与任何已知的毒力或抗生素抗性基因具有同源性。基因组分析表明,尽管观察到宿主菌株的快速复制和裂解,但JD419是一种温和噬菌体。随着合成生物学的最新进展,JD419可以通过基因工程进行修饰,去除与前噬菌体相关的基因,防止潜在的溶原性,以便作为治疗性噬菌体进行应用。