Tuberculosis (TB) continues to remain at the forefront of the infectious disease burden globally, albeit with some aberrations during the COVID-19 pandemic. Among many factors, the emergence of drug resistance or antimicrobial resistance (AMR) has necessitated a renewed focus on developing novel and repurposed drugs against TB. Host-directed therapy (HDT) has emerged as an attractive alternative and a complementary strategy to the conventional antibiotic-based therapy of tuberculosis since HDT enjoys the advantage of disarming the pathogen of its ability to develop drug resistance. Considering the imminent threat of AMR across the spectrum of bacterial pathogens, HDT promises to overcome the drug shortage against superbugs. While all these make HDT a very attractive strategy, identifying the right set of host targets to develop HDT remains a challenge, despite remarkable development in the field over the past decade. In this review, we examine the host mechanisms, that either inadvertently or through targeted perturbation by the pathogen, help TB pathogenesis, and we discuss the latest developments in the targeting of some of the key pathways to achieve newer TB therapeutics.

尽管在 COVID-19 大流行期间出现了一些异常情况，但结核病 (TB) 仍然是全球传染病负担的前列。在众多因素中，耐药性或抗菌素耐药性 (AMR) 的出现使得人们有必要重新关注开发新型和重新利用的结核病药物。宿主定向治疗 (HDT) 已成为传统的基于抗生素的结核病治疗的一种有吸引力的替代方案和补充策略，因为 HDT 具有解除病原体产生耐药性的能力的优势。考虑到 AMR 对各种细菌病原体造成的迫在眉睫的威胁，HDT 有望克服针对超级细菌的药物短缺问题。尽管所有这些使 HDT 成为一种非常有吸引力的策略，但确定开发 HDT 的正确宿主目标仍然是一个挑战，尽管该领域在过去十年中取得了显着的发展。在这篇综述中，我们检查了宿主机制，无论是无意中还是通过病原体的有针对性的扰动，有助于结核病的发病机制，并且我们讨论了一些关键途径的靶向以获得新的结核病治疗的最新进展。