Dataset Information

Lipid droplet proteomics of THP1 macrophages infected with Mycobacterium tuberculosis

ABSTRACT: Growing evidence suggests the importance of lipid metabolism in pathogenesis of tuberculosis. Neutral lipids form the majority of lipids in caseous granulomas characteristic of tuberculosis. Macrophage lipid droplets form the store house of these lipids, yet infection induced changes in the proteome of these dynamic organelles remains elusive. Here we employed quantitative proteomics to identify alterations induced upon infection with live Mycobacterium tuberculosis in comparison with heat killed bacilli and uninfected macrophages. Association of specific proteins coupled with lysosomal function was found to be increased upon infection with live M. tuberculosis. Biochemical and microscopy based evidence validated the enrichment of the small GTPase Arl8b, the guanine nucleotide effector LAMTOR1, and the scavenger receptor SCARB2 on lipid droplets during live Mtb infection. We validated the localization of Arl8b on lipid droplets using super-resolution microscopy. Increased abundance of these lysosomal proteins on lipid droplets upon infection with live Mtb suggests active manipulation of the host lipid droplets by the pathogen. Furthermore, depletion of lipid droplets upon stable knockdown of diacylglycerol O-acyltransferase led to reduction in lysosomal acidification of infected cells, suggesting an active role of lipid droplets in lysosomal function during infection.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Macrophage

DISEASE(S): Tuberculosis

SUBMITTER: Sheetal Gandotra

LAB HEAD: Sheetal Gandotra

PROVIDER: PXD008950 | Pride | 2019-11-14

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	KA_TMT_LDREPLICATES_MS3_020617.msf	Msf
	KA_TMT_LDREPLICATES_MS3_020617.pdResult	Other
	TMT_LC_Mtb_LD_KS_1.raw	Raw
	TMT_LC_Mtb_LD_KS_2.raw	Raw
	TMT_LC_Mtb_LD_KS_3.raw	Raw

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Publications

Quantitative Lipid Droplet Proteomics Reveals Mycobacterium tuberculosis Induced Alterations in Macrophage Response to Infection.

Menon Dilip D Singh Kaurab K Pinto Sneha M SM Nandy Ananya A Jaisinghani Neetika N Kutum Rintu R Dash Debasis D Prasad T S Keshava TSK Gandotra Sheetal S

ACS infectious diseases 20190204 4

Growing evidence suggests the importance of lipid metabolism in pathogenesis of tuberculosis. Neutral lipids form the majority of lipids in a caseous granuloma, a pathology characteristic of tuberculosis. Cytosolic lipid droplets (LDs) of macrophages form the store house of these lipids and have been demonstrated to contribute to the inflammatory response to infection. The proteome of lipid droplets reflects the mechanisms of lipid metabolism active under a condition. However, infection induced ...[more]

PMID: 30663302

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