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在人全血中鉴定噬菌体裂解活性以选择有效的治疗性噬菌体。

Characterization of Phage Lytic Activity in Human Whole Blood for the Selection of Efficient Therapeutic Phages.

机构信息

Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel.

出版信息

Viruses. 2021 Jan 11;13(1):89. doi: 10.3390/v13010089.

Abstract

The global increase in multidrug-resistant (MDR) pathogenic bacteria has led to growing interest in bacteriophage ("phage") therapy. Therapeutic phages are usually selected based on their ability to infect and lyse target bacteria, using in vitro assays. In these assays, phage infection is determined using target bacteria grown in standard commercial rich media, while evaluation of the actual therapeutic activity requires the presence of human blood. In the present work, we characterized the ability of two different lytic phages (ϕA1122 and PST) to infect and kill a luminescent EV76 strain suspended in Brain Heart Infusion (BHI)-rich medium or in human whole blood, simulating the host environment. We found that the ability of the phages to infect and lyse blood-suspended was not correlated with their ability to infect and lyse BHI-suspended bacteria. While the two different phages exhibited efficient infective capacity in a BHI-suspended culture, only the PST phage showed efficient lysis ability against blood-suspended bacteria. Therefore, we recommend that for personalized phage therapy, selection of phage(s) for efficient treatment of patients suffering from MDR bacterial infections should include prior testing of the candidate phage(s) for their lysis ability in the presence of human blood.

摘要

全球耐多药(MDR)病原菌的增加使得噬菌体(“phage”)治疗法越来越受到关注。治疗性噬菌体通常根据其感染和裂解目标细菌的能力,通过体外检测进行选择。在这些检测中,噬菌体的感染是通过在标准商业丰富培养基中生长的目标细菌来确定的,而对实际治疗活性的评估需要人血的存在。在本工作中,我们描述了两种不同的溶菌噬菌体(ϕA1122 和 PST)在脑心浸液(BHI)丰富培养基或人全血中悬浮的发光 EV76 菌株中感染和杀死的能力,模拟了宿主环境。我们发现噬菌体感染和裂解悬浮血的能力与它们感染和裂解 BHI 悬浮细菌的能力没有相关性。虽然两种不同的噬菌体在 BHI 悬浮培养物中表现出有效的感染能力,但只有 PST 噬菌体对悬浮血中的细菌表现出有效的裂解能力。因此,我们建议对于个性化噬菌体治疗,选择用于有效治疗患有 MDR 细菌感染的患者的噬菌体(s),应包括在存在人血的情况下对候选噬菌体(s)的裂解能力进行预先测试。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9519/7827537/78b0bf768dfb/viruses-13-00089-g001.jpg

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