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Comprising nearly 40% of its dry weight,\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      lipids\u2014such as mycolic acids, phthiocerol dimycocerosates (PDIM), trehalose dimycolate (TDM), and sulfolipids (SLs)\u2014play crucial roles in infection, immune evasion, intracellular persistence, granuloma formation, transmission, and drug resistance. These lipids modulate host-pathogen interactions by altering host membrane biophysics, hijacking phagosome maturation, and interfering with host immune pathways, including autophagy and inflammatory signaling. Upon inhalation,\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      surface lipids inhibit pulmonary surfactant function and mask pathogen-associated molecular patterns, facilitating uptake by permissive macrophage subsets. Intracellularly, lipoglycans like mannose-capped lipoarabinomannan block phagolysosome fusion, while PDIM and TDM promote phagosomal escape and subversion of vesicular trafficking. Lipid-mediated modulation of autophagy pathways further enhances bacterial survival within host cells. In addition to shaping host immune responses,\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      lipids orchestrate granuloma development and promote pathological features such as foam cell formation and caseation, which are central to transmission. Specifically, phenolic glycolipids and SLs stimulate neuronal pathways, triggering cough, thereby facilitating aerosol spread. Finally, the lipid-rich envelope acts as a formidable barrier to antibiotics, with resistance partly driven by the altered lipid composition and architecture in multidrug-resistant strains. Targeting lipid biosynthesis and transport pathways offers promising avenues for novel anti-TB therapies. This review highlights the multifaceted roles of\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      lipids at the host-pathogen interface, recent technical advances enabling these insights, and emerging challenges in translating lipid biology into improved TB control.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03959-25","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:00:41Z","timestamp":1770040841000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["The lipid language of tuberculosis:\n                    <i>Mycobacterium tuberculosis<\/i>\n                    surface molecules in host interaction and drug resistance"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7876-3322","authenticated-orcid":false,"given":"Sandhya Krishnan","family":"Radhakrishnan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Center for Biological Sciences","place":["Bangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-8518","authenticated-orcid":true,"given":"Varadharajan","family":"Sundaramurthy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Center for Biological Sciences","place":["Bangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","unstructured":"World Health Organization. 2024. Global tuberculosis report 2024. Geneva WHO. Available from: https:\/\/www.who.int\/teams\/global-programme-on-tuberculosis-and-lung-health\/tb-reports\/global-tuberculosis-report-2024. 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