Lipid metabolism in the resuscitation of dormant mycobacterium tuberculosis: molecular resilience, host hijacking, and clinical opportunities.

Latent infection and reactivation of Mycobacterium tuberculosis (Mtb) represent key obstacles to the global strategy to end tuberculosis. The 2024 ICE-TB international consensus redefined tuberculosis as a continuum of pathological states that includes subclinical forms, with lipid metabolism being the core mechanism driving Mtb's transition across different disease stages. This review systematically elucidates the molecular mechanisms by which Mtb maintains survival through lipidome remodelling under restrictive microenvironments (phosphate deprivation, oxidative stress), with a focus on the synergistic roles of key regulatory factors such as MtrA, DosR and OmamC in sensing environmental signals and initiating the reactivation process. At the host-pathogen interaction level, this paper discusses Mtb's pathogenic strategies, including the construction of a lipid-enriched microenvironment by hijacking lysosomal function through the secretion of 1-TbAd, and the induction of systemic insulin resistance via the PPE2 protein. Furthermore, this review evaluates the clinical utility of biomarkers based on lipid metabolic profiles in predicting the risk of relapse, providing a theoretical basis for the development of novel intervention strategies targeting lipid metabolic pathways.