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Revolutionizing control strategies against Mycobacterium tuberculosis infection through selected targeting of lipid metabolism

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Abstract

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.

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Acknowledgements

We thank both the associate editor and the reviewers for providing valuable feedback that enhanced the quality of this paper. MID (Medical Illustration & Design), a part of the Medical Research Support Services of Yonsei University College of Medicine, for providing excellent support with medical illustration.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government Ministry of Science and ICT (MSIT) (RS-2023-00208115) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare (HI22C0177), Republic of Korea.

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  1. 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

    Hagyu Kim & Sung Jae Shin

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Kim, H., Shin, S.J. Revolutionizing control strategies against Mycobacterium tuberculosis infection through selected targeting of lipid metabolism. Cell. Mol. Life Sci. 80, 291 (2023). https://doi.org/10.1007/s00018-023-04914-5

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