title: Quantitative Proteomics and Lipidomics Analysis of Endoplasmic Reticulum of Macrophage Infected with Mycobacterium tuberculosis.
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 specific roles of ER in understanding the cell biology of mycobacterial infection with special reference to the impact of host response.
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India ; School of Life Sciences, Jaipur National University, Jaipur 302025, India.
authors.forename: Najmuddin Mohd
authors.initials: NM
authors.lastname: Saquib
authors.affiliation: Drug Discovery Research Centre, Translational Health Science & Technology Institute, Gurgaon 122016, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Jamwal
authors.affiliation: Drug Discovery Research Centre, Translational Health Science & Technology Institute, Gurgaon 122016, India.
authors.forename: Mukul Kumar
authors.initials: MK
authors.lastname: Midha
authors.affiliation: School of Life Sciences, Jaipur National University, Jaipur 302025, India.
authors.forename: Hirdya Narain
authors.initials: HN
authors.lastname: Verma
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India ; Drug Discovery Research Centre, Translational Health Science & Technology Institute, Gurgaon 122016, India.
authors.forename: Venkatasamy
authors.initials: V
authors.lastname: Manivel