Quantitative Proteomics and Lipidomics Analysis of Endoplasmic Reticulum of Macrophage Infected with Mycobacterium tuberculosis

International Journal of Proteomics
Najmuddin Mohd SaquibVenkatasamy Manivel

Abstract

Even though endoplasmic reticulum (ER) stress associated with mycobacterial infection has been well studied, the molecular basis of ER as a crucial organelle to determine the fate of Mtb is yet to be established. Here, we have studied the ability of Mtb to manipulate the ultrastructural architecture of macrophage ER and found that the ER-phenotypes associated with virulent (H37Rv) and avirulent (H37Ra) strains were different: a rough ER (RER) with the former against a smooth ER (SER) with the later. Further, the functional attributes of these changes were probed by MS-based quantitative proteomics (133 ER proteins) and lipidomics (8 phospholipids). Our omics approaches not only revealed the host pathogen cross-talk but also emphasized how precisely Mtb uses proteins and lipids in combination to give rise to characteristic ER-phenotypes. H37Ra-infected macrophages increased the cytosolic Ca(2+) levels by attenuating the ATP2A2 protein and simultaneous induction of PC/PE expression to facilitate apoptosis. However, H37Rv inhibited apoptosis and further controlled the expression of EST-1 and AMRP proteins to disturb cholesterol homeostasis resulting in sustained infection. This approach offers the potential to decipher the specifi...Continue Reading

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Citations

Mar 17, 2016·Tuberculosis·Yongyong CuiXiangmei Zhou
Oct 31, 2017·Molecular BioSystems·Arumugam KamaladeviKrishnaswamy Balamurugan
Jan 28, 2018·Clinical and Translational Medicine·Todd A Lydic, Young-Hwa Goo
May 13, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·Adam LamSaurabh Aggarwal
Sep 19, 2019·PLoS Computational Biology·Ryan S McClureJason E McDermott
Feb 27, 2018·Frontiers in Immunology·Susanta PahariJaved N Agrewala
Mar 25, 2017·Frontiers in Cellular and Infection Microbiology·Pei LiChen Tan
Dec 27, 2016·Frontiers in Cellular and Infection Microbiology·Yongyong CuiXiangmei Zhou

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Methods Mentioned

BETA
protein folding
transmission electron microscopy
PMA
confocal microscopy

Software Mentioned

Image
ProteinPilot
Pro Plus
Odyssey
ProtScore

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis