NRF-DST Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Cytometry A. 2020 Jul;97(7):683-693. doi: 10.1002/cyto.a.24030. Epub 2020 May 21.
The ability of the bacterial pathogen Mycobacterium tuberculosis to adapt and survive within human cells to disseminate to other individuals and cause active disease is poorly understood. Research supports that as M. tuberculosis adapts to stressors encountered in the host, it exhibits variable physiological and metabolic states that are time and niche-dependent. Challenges associated with effective treatment and eradication of tuberculosis (TB) are in part attributed to our lack of understanding of these different mycobacterial phenotypes. This is mainly due to a lack of suitable tools to effectively identify/detect heterogeneous bacterial populations, which may include small, difficult-to-culture subpopulations. Importantly, flow cytometry allows rapid and affordable multiparametric measurements of physical and chemical characteristics of single cells, without the need to preculture cells. Here, we summarize current knowledge of flow cytometry applications that have advanced our understanding of the physiology of M. tuberculosis during TB disease. Specifically, we review how host-associated stressors influence bacterial characteristics such as metabolic activity, membrane potential, redox status and the mycobacterial cell wall. Further, we highlight that flow cytometry offers unprecedented opportunities for insight into bacterial population heterogeneity, which is increasingly appreciated as an important determinant of disease outcome. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
细菌病原体结核分枝杆菌在人体细胞内适应和生存、传播给其他人并引起活动性疾病的能力尚未被充分理解。研究表明，随着结核分枝杆菌适应宿主中遇到的应激源，它表现出随时间和生态位变化的不同生理和代谢状态。有效治疗和根除结核病（TB）面临的挑战部分归因于我们对这些不同的分枝杆菌表型缺乏了解。这主要是由于缺乏有效的工具来有效识别/检测异质细菌群体，其中可能包括难以培养的小亚群。重要的是，流式细胞术允许快速且经济实惠地对单个细胞的物理和化学特性进行多参数测量，而无需预先培养细胞。在这里，我们总结了流式细胞术应用的现有知识，这些知识增进了我们对结核分枝杆菌在结核病期间的生理学的理解。具体而言，我们回顾了宿主相关应激源如何影响细菌特性，如代谢活性、膜电位、氧化还原状态和分枝杆菌细胞壁。此外，我们强调流式细胞术为深入了解细菌群体异质性提供了前所未有的机会，因为细菌群体异质性越来越被认为是疾病结局的一个重要决定因素。©2020 作者。流式细胞术由 Wiley 期刊出版公司代表国际细胞分析协会出版。
