{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:47:43Z","timestamp":1785937663631,"version":"3.56.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Latent infection and reactivation of Mycobacterium tuberculosis (\n                    <jats:italic>Mtb<\/jats:italic>\n                    ) 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\n                    <jats:italic>Mtb<\/jats:italic>\n                    \u2019s transition across different disease stages. This review systematically elucidates the molecular mechanisms by which\n                    <jats:italic>Mtb<\/jats:italic>\n                    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\n                    <jats:italic>Mtb<\/jats:italic>\n                    \u2019s 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.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1838865","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:13:14Z","timestamp":1785935594000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid metabolism in the resuscitation of dormant mycobacterium tuberculosis: molecular resilience, host hijacking, and clinical opportunities"],"prefix":"10.3389","volume":"16","author":[{"given":"Chunze","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Dazhou Integrated Traditional Chinese Medicine & Western Medicine Hospital, Dazhou Second People\u2019s Hospital","place":["Dazhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Dazhou Integrated Traditional Chinese Medicine & Western Medicine Hospital, Dazhou Second People\u2019s Hospital","place":["Dazhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Dazhou Integrated Traditional Chinese Medicine & Western Medicine Hospital, Dazhou Second People\u2019s Hospital","place":["Dazhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Dazhou Integrated Traditional Chinese Medicine & Western Medicine Hospital, Dazhou Second People\u2019s Hospital","place":["Dazhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Dazhou Integrated Traditional Chinese Medicine & Western Medicine Hospital, Dazhou Second People\u2019s Hospital","place":["Dazhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17665","DOI":"10.1038\/s41598-017-17751-x","article-title":"The transcriptome of Mycobacterium tuberculosis in a lipid-rich dormancy model through RNAseq analysis","volume":"7","author":"Aguilar-Ayala","year":"2017","journal-title":"Sci. Rep."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10091821","article-title":"Mycobacterium tuberculosis whiB3 and lipid metabolism genes are regulated by host induced oxidative stress","volume":"10","author":"Barrientos","year":"2022","journal-title":"Microorganisms"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI161944","article-title":"A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages","volume":"133","author":"Bedard","year":"2023","journal-title":"J. Clin. Invest."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k2738","article-title":"Revisiting the timetable of tuberculosis","volume":"362","author":"Behr","year":"2018","journal-title":"BMJ (Clinical Res. ed.)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e553","DOI":"10.1093\/infdis\/jiae523","article-title":"Troglitazone reduction of intracellular Mycobacterium tuberculosis survival via macrophage autophagy through LKB1-AMPK\u03b1 signaling","volume":"231","author":"Bi","year":"2025","journal-title":"J. Infect. Dis."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.109532.1","article-title":"The PPE2 protein of Mycobacterium tuberculosis is responsible for the development of hyperglycemia and insulin resistance during tuberculosis","volume":"15","author":"Bisht","year":"2026","journal-title":"eLife"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136222","article-title":"The knowns and unknowns of latent Mycobacterium tuberculosis infection","volume":"131","author":"Boom","year":"2021","journal-title":"J. Clin. Invest."},{"key":"B8","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1038\/s41589-019-0336-0","article-title":"Mycobacterium tuberculosis releases an antacid that remodels phagosomes","volume":"15","author":"Buter","year":"2019","journal-title":"Nat. Chem. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/s41579-022-00763-4","article-title":"Immune evasion and provocation by Mycobacterium tuberculosis","volume":"20","author":"Chandra","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41392-020-00427-w","article-title":"Novel therapeutic evaluation biomarkers of lipid metabolism targets in uncomplicated pulmonary tuberculosis patients","volume":"6","author":"Chen","year":"2021","journal-title":"Signal. Transduction Targeting Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"40881","DOI":"10.1038\/s41598-025-24714-0","article-title":"Benchtop NMR urine metabolomics for diagnosing pulmonary tuberculosis","volume":"15","author":"Comella-Del-Barrio","year":"2025","journal-title":"Sci. Rep."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2024.2437242","article-title":"Predictive metabolite signatures for risk of progression to active TB from QuantiFERON supernatants of household contacts of TB patients","volume":"14","author":"Daniel","year":"2025","journal-title":"Emerg. Microbes Infect."},{"key":"B13","doi-asserted-by":"publisher","first-page":"381","DOI":"10.5588\/ijtld.24.0081","article-title":"The international consensus for early TB framework (ICE-TB): implications from a low-incidence setting","volume":"28","author":"Denholm","year":"2024","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.01530-24","article-title":"Proteomic characterization of Mycobacterium tuberculosis subjected to carbon starvation","volume":"10","author":"Devlin","year":"2025","journal-title":"mSystems"},{"key":"B15","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1186\/s40001-025-02768-0","article-title":"Exploring T-cell metabolism in tuberculosis: development of a diagnostic model using metabolic genes","volume":"30","author":"Ding","year":"2025","journal-title":"Eur. J. Med. Res."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1617292","article-title":"Inhibition of CYP450 family 1 subfamily B member 1 (CYP1B1) expression in macrophage reduces the inflammatory response in type 2 diabetes mellitus combined with tuberculosis","volume":"16","author":"Du","year":"2025","journal-title":"Front. Endocrinol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.82469","article-title":"Estimating the contribution of subclinical tuberculosis disease to transmission: an individual patient data analysis from prevalence surveys","volume":"12","author":"Emery","year":"2023","journal-title":"eLife"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1630603","article-title":"Recent advances in biomarkers for diabetes mellitus and tuberculosis comorbidity: a comprehensive review","volume":"16","author":"Fang","year":"2025","journal-title":"Front. Endocrinol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e830","DOI":"10.1093\/cid\/ciaa1402","article-title":"Subclinical tuberculosis disease\u2014a review and analysis of prevalence surveys to inform definitions, burden, associations, and screening methodology","volume":"73","author":"Frascella","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02839","article-title":"MtrA response regulator controls cell division and cell wall metabolism and affects susceptibility of mycobacteria to the first line antituberculosis drugs","volume":"9","author":"Gorla","year":"2018","journal-title":"Front. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"11317","DOI":"10.1038\/s41467-025-66437-w","article-title":"Mycobacterium tuberculosis overcomes phosphate starvation by extensively remodelling its lipidome with phosphorus-free lipids","volume":"16","author":"Gray","year":"2025","journal-title":"Nat. Commun."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002152","article-title":"The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling","volume":"13","author":"Houben","year":"2016","journal-title":"PloS Med."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46477","article-title":"Persistent inflammation during anti-tuberculosis treatment with diabetes comorbidity","volume":"8","author":"Kumar","year":"2019","journal-title":"eLife"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1329715","article-title":"Roles of lipolytic enzymes in Mycobacterium tuberculosis pathogenesis","volume":"15","author":"Lin","year":"2024","journal-title":"Front. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1409552","article-title":"Individualized lipid profile in urine-derived extracellular vesicles from clinical patients with Mycobacterium tuberculosis infections","volume":"15","author":"Lyu","year":"2024","journal-title":"Front. Microbiol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305592","article-title":"Single-cell sequencing reveals functional alterations in tuberculosis","volume":"11","author":"Lyu","year":"2024","journal-title":"Advanced Sci. (Weinheim Baden-Wurttemberg Germany)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.freeradbiomed.2018.11.032","article-title":"Mycobacterium tuberculosis WhiB3 maintains redox homeostasis and survival in response to reactive oxygen and nitrogen species","volume":"131","author":"Mehta","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"19084","DOI":"10.1039\/d4sc06618a","article-title":"Decoding the role of mycobacterial lipid remodelling and membrane dynamics in antibiotic tolerance","volume":"15","author":"Menon","year":"2024","journal-title":"Chem. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"797","DOI":"10.5588\/ijtld.21.0425","article-title":"Clinical standards for the assessment, management and rehabilitation of post-TB lung disease","volume":"25","author":"Migliori","year":"2021","journal-title":"Int. J. Tuberculosis Lung Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1080\/15548627.2021.1936355","article-title":"Epigenetic reader BRD4 supports mycobacterial pathogenesis by co-modulating host lipophagy and angiogenesis","volume":"18","author":"Mukherjee","year":"2022","journal-title":"Autophagy"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/msphere.00141-26","article-title":"Systems analysis reveals alternate metabolic states adopted by Mycobacterium tuberculosis across species","author":"Padilla-Gomez","year":"2025","journal-title":"mSphere"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112875","article-title":"MtrA modulates Mycobacterium tuberculosis cell division in host microenvironments to mediate intrinsic resistance and drug tolerance","volume":"42","author":"Peterson","year":"2023","journal-title":"Cell Rep."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.633360","article-title":"Regulatory mechanisms of autophagy-targeted antimicrobial therapeutics against mycobacterial infection","volume":"11","author":"Silwal","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000545","article-title":"Mycobacterium tuberculosis WhiB3 maintains redox homeostasis by regulating virulence lipid anabolism to modulate macrophage response","volume":"5","author":"Singh","year":"2009","journal-title":"PloS Pathog."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.03208-23","article-title":"Genetic factors affecting storage and utilization of lipids during dormancy in Mycobacterium tuberculosis","volume":"15","author":"Sturm","year":"2024","journal-title":"mBio"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06592-6","article-title":"Plasma proteomic associations with genetics and health in the UK Biobank","volume":"622","author":"Sun","year":"2023","journal-title":"Nature."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1526740","article-title":"Metabolomics and lipidomics of plasma biomarkers for tuberculosis diagnostics using UHPLC-HRMS","volume":"15","author":"Sun","year":"2025","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1079569","article-title":"Tuberculosis: the success tale of less explored dormant Mycobacterium tuberculosis","volume":"12","author":"Verma","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00577-23","article-title":"Integration of metabolomics and transcriptomics reveals major metabolic pathways and potential biomarkers involved in pulmonary tuberculosis and pulmonary tuberculosis-complicated diabetes","volume":"11","author":"Wang","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1038\/s41579-025-01201-x","article-title":"Mycobacterium tuberculosis biology, pathogenicity and interaction with the host","volume":"23","author":"Warner","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"B41","unstructured":"Global Tuberculosis Report 2025\n          \n          2025"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1013810","article-title":"Mycobacterium tuberculosis manipulates LINC02528 in macrophages to modulate anti-tuberculosis metabolic immunity","volume":"21","author":"Xu","year":"2025","journal-title":"PLoS Pathog."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S558880","article-title":"Lipidomics-Based Identification of Plasma Lipid Biomarkers in Tuberculosis-Coronary Artery Disease Comorbidity","volume":"18","author":"Zhao","year":"2025","journal-title":"Infect. Drug Resist."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012205","article-title":"Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection","volume":"20","author":"Zheng","year":"2024","journal-title":"PLoS Pathog."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70559","article-title":"Robust diagnostic and therapeutic biomarkers for tuberculosis identified through multi-omics and Mendelian randomization analysis","volume":"7","author":"Zhu","year":"2025","journal-title":"MedComm"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1838865\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:13:16Z","timestamp":1785935596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1838865\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":45,"alternative-id":["10.3389\/fcimb.2026.1838865"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1838865","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"article-number":"1838865"}}