
@article {164006,
	title = {The lipid language of tuberculosis:  surface molecules in host interaction and drug resistance.},
	journal = {mBio},
	year = {2026},
	month = {2026 Feb 02},
	pages = {e0395925},
	abstract = {<p class="rtejustify">(), the causative agent of tuberculosis (TB), is a uniquely successful pathogen due in large part to its complex lipid-rich cell envelope. Comprising nearly 40\% of its dry weight, lipids-such as mycolic acids, phthiocerol dimycocerosates (PDIM), trehalose dimycolate (TDM), and sulfolipids (SLs)-play 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, 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, 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 lipids at the host-pathogen interface, recent technical advances enabling these insights, and emerging challenges in translating lipid biology into improved TB control.</p>
},
	keywords = {cell wall, Host-Pathogen Interactions, Mtb lipids, multidrug resistance, Mycobacterium tuberculosis, pathogenesis.},
	issn = {2150-7511},
	doi = {10.1128/mbio.03959-25},
	url = {https://pubmed.ncbi.nlm.nih.gov/41627032/},
	author = {Radhakrishnan, Sandhya Krishnan and Sundaramurthy, Varadharajan}
}
@article {157492,
	title = {M. tuberculosis surface sulfoglycolipid SL-1 activates the mechanosensitive channel TRPV4 to enhance lysosomal biogenesis and exocytosis in macrophages},
	journal = {Mol Biol Cell},
	volume = {36},
	year = {2025},
	month = {2025 Jun 01},
	pages = {ar76},
	abstract = {<p>Intracellular pathogens manipulate host cellular pathways to ensure their survival. (Mtb) disrupts phagosomal trafficking to prevent fusion with lysosomes. Beyond this localized effect, Mtb globally remodels the host lysosomal system, predominantly through its virulence-associated surface lipid, sulfolipid-1 (SL-1). SL-1 enhances lysosomal biogenesis via the mTORC1-TFEB axis; however, the upstream mediators remain unknown. Here, we show that SL-1 induces calcium influx into macrophages and identify the mechanosensitive calcium channel transient receptor potential vanilloid subtype 4 (TRPV4) as a crucial upstream mediator of SL-1-induced lysosomal remodeling. TRPV4 influences multiple aspects of lysosomal function, including biogenesis, acidification, enzymatic activity, phagosome maturation, and lysosomal exocytosis. These effects are recapitulated during Mtb infection, underscoring the relevance of SL-1- and TRPV4-dependent lysosomal remodeling in an infection context. TRPV4 expression is upregulated during Mtb infection and partially localizes to both lysosomes and the Mtb-containing vacuole. Remarkably, TRPV4 activation, independent of SL-1, is sufficient to enhance lysosomal biogenesis, identifying TRPV4 as a key regulator of lysosomal homeostasis. Together, these findings uncover a novel mechanism of lysosomal remodeling driven by a pathogen lipid virulence factor and reveal a previously unrecognized role for TRPV4 in modulating lysosomal homeostasis in macrophages.</p>
},
	keywords = {Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Calcium, Exocytosis, Glycolipids, Humans, Lysosomes, Macrophages, Mice, Mice, Inbred C57BL, Mycobacterium tuberculosis, Phagosomes, TRPV Cation Channels},
	issn = {1939-4586},
	doi = {10.1091/mbc.E24-12-0560},
	url = {https://www.molbiolcell.org/doi/10.1091/mbc.E24-12-0560?url_ver=Z39.88-2003\&rfr_id=ori:rid:crossref.org\&rfr_dat=cr_pub\%20\%200pubmed},
	author = {Umar, Ibrahim and Gulzar, Shah-E-Jahan and Sundaramurthy, Varadharajan}
}
