Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Front Immunol. 2021 Jun 24;12:665785. doi: 10.3389/fimmu.2021.665785. eCollection 2021.
Tuberculosis (TB) remains a challenging global health concern and claims more than a million lives every year. We lack an effective vaccine and understanding of what constitutes protective immunity against TB to inform rational vaccine design. Moreover, treatment of TB requires prolonged use of multi-drug regimens and is complicated by problems of compliance and drug resistance. While most (Mtb) bacilli are quickly killed by the drugs, the prolonged course of treatment is required to clear persistent drug-tolerant subpopulations. Mtb's differential sensitivity to drugs is, at least in part, determined by the interaction between the bacilli and different host macrophage populations. Therefore, to design better treatment regimens for TB, we need to understand and modulate the heterogeneity and divergent responses that Mtb bacilli exhibit within macrophages. However, developing drugs is a long and expensive process. An alternative approach to expedite the development of new TB treatments is to repurpose existing drugs that were developed for other therapeutic purposes if they also possess anti-tuberculosis activity. There is growing interest in the use of immune modulators to supplement current anti-TB drugs by enhancing the host's antimycobacterial responses. Ion channel blocking agents are among the most promising of the host-directed therapeutics. Some ion channel blockers also interfere with the activity of mycobacterial efflux pumps. In this review, we discuss some of the ion channel blockers that have shown promise as potential anti-TB agents.
结核病（TB）仍然是一个具有挑战性的全球健康问题，每年导致超过 100 万人死亡。我们缺乏有效的疫苗，也不了解什么是对结核病的保护性免疫，无法为合理的疫苗设计提供信息。此外，结核病的治疗需要长期使用多种药物方案，并且存在依从性和耐药性问题。虽然大多数（Mtb）杆菌很快被药物杀死，但需要延长治疗过程以清除持续存在的耐药亚群。Mtb 对药物的不同敏感性至少部分取决于杆菌与不同宿主巨噬细胞群体之间的相互作用。因此，为了设计更好的结核病治疗方案，我们需要了解和调节 Mtb 杆菌在巨噬细胞内表现出的异质性和不同反应。然而，开发药物是一个漫长而昂贵的过程。如果现有的用于其他治疗目的的药物也具有抗结核活性，那么重新利用这些药物是加速新的结核病治疗方法开发的一种替代方法。人们越来越感兴趣地使用免疫调节剂来通过增强宿主的抗分枝杆菌反应来补充当前的抗 TB 药物。离子通道阻滞剂是最有前途的宿主定向治疗药物之一。一些离子通道阻滞剂也干扰分枝杆菌外排泵的活性。在这篇综述中，我们讨论了一些已显示出作为潜在抗结核药物的希望的离子通道阻滞剂。
