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

Authors
  • Menon, Dilip1, 2
  • Singh, Kaurab1, 2
  • Pinto, Sneha M3
  • Nandy, Ananya1, 2
  • Jaisinghani, Neetika1, 2
  • Kutum, Rintu4, 2
  • Dash, Debasis4, 2
  • Prasad, T S Keshava3, 5
  • Gandotra, Sheetal1, 2
  • 1 Cardiorespiratory Disease Biology , CSIR-Institute of Genomics and Integrative Biology , Sukhdev Vihar, Mathura Road , New Delhi 110025 , India. , (India)
  • 2 Academy of Scientific and Innovative Research (AcSIR) , Ghaziabad 201002 , India. , (India)
  • 3 Center for Systems Biology and Molecular Medicine , Yenepoya Research Center, Yenepoya (Deemed to be University) , Mangalore 575018 , India. , (India)
  • 4 Informatics and Big Data , CSIR-Institute of Genomics and Integrative Biology , Sukhdev Vihar, Mathura Road , New Delhi 110025 , India. , (India)
  • 5 Institute of Bioinformatics , International Technology Park , Bangalore 560066 , India. , (India)
Type
Published Article
Journal
ACS Infectious Diseases
Publisher
American Chemical Society
Publication Date
Apr 12, 2019
Volume
5
Issue
4
Pages
559–569
Identifiers
DOI: 10.1021/acsinfecdis.8b00301
PMID: 30663302
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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 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 (Mtb) in comparison with heat killed bacilli or uninfected macrophages. We found increased abundance of proteins coupled with lipid metabolism, protein synthesis, and vesicular transport function in LDs upon infection with live Mtb. Using biochemical methods and microscopy, we validated ADP-ribosyltransferase (Arf)-like 8 (ARL8B) to be increased on the lipid droplet surface of live Mtb infected macrophages and that ARL8B is a bonafide LD protein. This study provides the first proteomic evidence that the dynamic responses to infection also encompass changes at the level of LDs. This information will be important in understanding how Mtb manipulates lipid metabolism and defense mechanisms of the host macrophage.

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