Intracellular pathogens interact with host systems in intimate ways to sustain a pathogenic lifestyle. Consequently, these interactions can potentially be targets of host-directed interventions against infectious diseases. In case of tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), while effective anti-tubercular compounds are available, the long treatment duration and emerging drug resistance necessitate identification of new class of molecules with anti-TB activity, as well as new treatment strategies. A significant part of the effort in finding new anti-TB drugs is focused on bacterial targets in bacterial systems. However, the host environment plays a major role in pathogenesis mechanisms and must be considered actively in these efforts. On the one hand, the bacterial origin targets must be relevant and accessible in the host, while on the other hand, new host origin targets required for the bacterial survival can be targeted. Such targets are good candidates for host-directed therapeutics, a strategy gaining traction as an adjunct in TB treatment. In this review, we will summarise the screening platforms used to identify compounds with anti-tubercular activities inside different host environments and outline recent technical advances in these platforms. Finally, while the examples given are specific to mycobacteria, the methods and principles outlined are broadly applicable to most intracellular infections.

中文翻译：

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基于宿主筛选具有细胞内抗分枝杆菌活性的化合物的进展

细胞内病原体以亲密的方式与宿主系统相互作用，以维持致病的生活方式。因此，这些相互作用可能成为针对传染病的宿主导向干预的目标。如果是由结核分枝杆菌( Mtb ) 引起的结核病 (TB))，虽然有效的抗结核化合物是可用的，但长期的治疗持续时间和新出现的耐药性需要鉴定具有抗结核活性的新型分子，以及新的治疗策略。寻找新的抗结核药物的工作的一个重要部分集中在细菌系统中的细菌靶点上。然而，宿主环境在发病机制中起着重要作用，在这些努力中必须积极考虑。一方面，细菌来源目标必须在宿主中相关且可访问，而另一方面，可以针对细菌存活所需的新宿主来源目标。这些目标是宿主导向疗法的良好候选者，这种策略作为结核病治疗的辅助手段而受到关注。在这次审查中，我们将总结用于识别不同宿主环境中具有抗结核活性的化合物的筛选平台，并概述这些平台的最新技术进展。最后，虽然给出的例子是针对分枝杆菌的，但所概述的方法和原则广泛适用于大多数细胞内感染。