Quantitative Proteomics and Lipidomics Analysis of Endoplasmic Reticulum of Macrophage Infected withMycobacterium tuberculosis

International Journal of Proteomics

Mukul KumarMidha¹  Hirdya NarainVerma¹  Najmuddin MohdSaquib¹  ShilpaJamwal¹  VenkatasamyManivel¹ 

DOI  :  10.1155/2015/270438

学科分类：生物化学/生物物理

来源: Hindawi Publishing Corporation

【 摘 要 】

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 ofMtbis yet to be established. Here, we have studied the ability ofMtbto 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 preciselyMtbuses proteins and lipids in combination to give rise to characteristic ER-phenotypes. H37Ra-infected macrophages increased the cytosolic Ca2+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.

【 授权许可】

Unknown