Rapid assessment of changes in phage bioactivity using dynamic light scattering.
Rapid assessment of changes in phage bioactivity using dynamic light scattering.
复制标题
使用动态光散射快速评估噬菌体生物活性的变化。
DOI：
10.1101/2023.07.02.547396
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Chang
中科院分区：
文献类型：
--
作者：
Dharmaraj,Tejas;Kratochvil,MichaelJ;Pourtois,JulieD;Chen,Qingquan;Hajfathalian,Maryam;Hargil,Aviv;Lin,Yung-Hao;Evans,Zoe;Oromí-Bosch,Agnès;Berry,JoelD;McBride,Robert;Haddock,NaomiL;Holman,DerekR;vanBelleghem,JonasD;Chang
正在进行广泛的努力来开发噬菌体作为针对耐药性细菌的疗法。然而，这些努力被噬菌体制剂的不稳定性和缺乏合适的工具来评估随时间的活性噬菌体浓度所混淆。在这项研究中，我们使用动态光散射（DLS）来测量响应于环境因素和时间的噬菌体物理状态的变化，发现噬菌体倾向于衰变并形成聚集体，并且聚集的程度可以用来预测噬菌体的生物活性。然后，我们使用DLS来优化来自人类临床试验的噬菌体储存条件，预测50年历史档案库中的生物活性，并评估用于噬菌体治疗/伤口感染模型的噬菌体样品。我们还提供了一个网络应用程序（噬菌体裂解功能估计），以促进DLS研究的细菌。我们的结论是，DLS提供了一个快速，方便，无损的工具，在学术和商业环境中的噬菌体制剂的质量控制。
Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. In this study, we use dynamic light scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-y-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web application (Phage-Estimator of Lytic Function) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and nondestructive tool for quality control of phage preparations in academic and commercial settings.