Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA
Appl Environ Microbiol. 2019 Apr 18;85(9). doi: 10.1128/AEM.00003-19. Print 2019 May 1.
Lytic bacteriophages (or phages) drive bacterial mortality by elaborating exquisite abilities to bind, breach, and destroy bacterial cell membranes and subjugate critical bacterial cell functions. These antimicrobial activities make phages ideal candidates to serve as, or provide sources of, biological control measures for bacterial pathogens. In this study, we isolated the phage vB_BanS_Bcp1 (here referred to as Bcp1) from landfill soil, using a host. The antimicrobial activities of both Bcp1 and its encoded endolysin, PlyB, were examined across different group species, including , , and , with pathogenic potential in humans and multiple different uses in biotechnological applications. The Bcp1 phage infected only a subset (11 to 66%) of each species group tested. In contrast, functional analysis of purified PlyB revealed a potent bacteriolytic activity against all isolates tested ( = 79). PlyB was, furthermore, active across broad temperature, pH, and salt ranges, refractory to the development of resistance, bactericidal as a single agent, and synergistic with a second endolysin, PlyG. To confirm the potential for PlyB as an antimicrobial agent, we demonstrated the efficacy of a single intravenous treatment with PlyB alone or combination with PlyG in a murine model of lethal infection. Overall, our findings show exciting potential for the Bcp1 bacteriophage and the PlyB endolysin as potential new additions to the antimicrobial armamentarium. Organisms of the lineage are ubiquitous in the environment and are responsible for toxin-mediated infections ranging from severe food poisoning () to anthrax (). The increasing incidence of many of these infections, combined with the specter of antibiotic resistance, has created a need for novel antimicrobials with potent activity, including bacteriophages (or phages) and phage-encoded products (i.e., endolysins). In this study, we describe a broadly infective phage, Bcp1, and its encoded endolysin, PlyB, which exhibited a rapidly bacteriolytic effect against all isolates tested with no evidence of evolving resistance. Importantly, PlyB was highly efficacious in a mouse model of lethal bacteremia with Both the Bcp1 phage and the PlyB endolysin represent novel mechanisms of action compared to antibiotics, with potential applications to address the evolving problem of antimicrobial resistance.
裂解性噬菌体（或噬菌体）通过精细的结合、穿透和破坏细菌细胞膜以及征服细菌关键细胞功能的能力，导致细菌死亡。这些抗菌活性使噬菌体成为细菌病原体的生物防治措施的理想候选物或提供来源。在这项研究中，我们使用宿主从垃圾填埋场土壤中分离出噬菌体 vB_BanS_Bcp1（以下简称 Bcp1）。我们检测了 Bcp1 及其编码的内溶素 PlyB 在不同的组物种中的抗菌活性，包括 、 、 和 ，这些物种在人类中具有致病性，并在生物技术应用中有多种不同用途。Bcp1 噬菌体仅感染所测试的每个 组物种的一部分（11% 到 66%）。相比之下，纯化的 PlyB 的功能分析显示出对所有测试的 分离株（=79）的强大溶菌活性。PlyB 还在广泛的温度、pH 和盐范围内具有活性，不易产生耐药性，作为单一药物具有杀菌作用，并且与第二种内溶素 PlyG 协同作用。为了确认 PlyB 作为抗菌剂的潜力，我们在致命 感染的小鼠模型中证明了单独使用 PlyB 或与 PlyG 联合治疗的疗效。总体而言，我们的研究结果表明，Bcp1 噬菌体和 PlyB 内溶素具有作为新的抗菌手段的令人兴奋的潜力。 谱系的生物体在环境中无处不在，它们负责从严重的食物中毒（）到炭疽（）的毒素介导的感染。这些感染中的许多感染的发生率不断增加，加上抗生素耐药性的出现，已经需要具有强大活性的新型抗菌药物，包括噬菌体（或噬菌体）和噬菌体编码的产物（即内溶素）。在这项研究中，我们描述了一种广泛感染的噬菌体 Bcp1 及其编码的内溶素 PlyB，它们对所有测试的 分离株均表现出快速溶菌作用，并且没有证据表明出现耐药性。重要的是，PlyB 在致命菌血症的小鼠模型中非常有效。Bcp1 噬菌体和 PlyB 内溶素都代表了与抗生素相比的新型作用机制，具有解决不断发展的抗菌耐药性问题的潜在应用。
