Department of Microbiology, Institute for Immunology and Immunological Disease, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea.
Cell Mol Life Sci. 2023 Sep 14;80(10):291. doi: 10.1007/s00018-023-04914-5.
Lipid species play a critical role in the growth and virulence expression of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). During Mtb infection, foamy macrophages accumulate lipids in granulomas, providing metabolic adaptation and survival strategies for Mtb against multiple stresses. Host-derived lipid species, including triacylglycerol and cholesterol, can also contribute to the development of drug-tolerant Mtb, leading to reduced efficacy of antibiotics targeting the bacterial cell wall or transcription. Transcriptional and metabolic analyses indicate that lipid metabolism-associated factors of Mtb are highly regulated by antibiotics and ultimately affect treatment outcomes. Despite the well-known association between major antibiotics and lipid metabolites in TB treatment, a comprehensive understanding of how altered lipid metabolites in both host and Mtb influence treatment outcomes in a drug-specific manner is necessary to overcome drug tolerance. The current review explores the controversies and correlations between lipids and drug efficacy in various Mtb infection models and proposes novel approaches to enhance the efficacy of anti-TB drugs. Moreover, the review provides insights into the efficacious control of Mtb infection by elucidating the impact of lipids on drug efficacy. This review aims to improve the effectiveness of current anti-TB drugs and facilitate the development of innovative therapeutic strategies against Mtb infection by making reverse use of Mtb-favoring lipid species.
脂质种类在结核分枝杆菌（Mtb）的生长和毒力表达中起着关键作用，Mtb 是结核病（TB）的病原体。在 Mtb 感染期间，泡沫状巨噬细胞在肉芽肿中积累脂质，为 Mtb 提供代谢适应和生存策略，以应对多种压力。宿主来源的脂质种类，包括三酰甘油和胆固醇，也可以促进耐药 Mtb 的发展，导致针对细菌细胞壁或转录的抗生素疗效降低。转录和代谢分析表明，Mtb 的脂质代谢相关因素受抗生素的高度调控，最终影响治疗结果。尽管在 TB 治疗中主要抗生素和脂质代谢物之间存在众所周知的关联，但全面了解宿主和 Mtb 中脂质代谢物的变化如何以特定药物的方式影响治疗结果，对于克服药物耐受性是必要的。本综述探讨了不同 Mtb 感染模型中脂质与药物疗效之间的争议和相关性，并提出了增强抗结核药物疗效的新方法。此外，该综述通过阐明脂质对药物疗效的影响，为有效控制 Mtb 感染提供了新的思路。本综述旨在通过反向利用有利于 Mtb 的脂质种类来提高现有抗结核药物的疗效，并促进针对 Mtb 感染的创新治疗策略的发展。
