文章基本信息

标题：M. tuberculosis Secretory Protein ESAT-6 Induces Metabolic Flux Perturbations to Drive Foamy Macrophage Differentiation
本地全文：下载
作者：Varshneya Singh ; Charanpreet Kaur ; Vijay K. Chaudhary 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
期号：1
DOI：10.1038/srep12906
语种：English
出版社：Springer Nature
摘要：The Foamy Macrophage (FM) differentiation forms a major component of the host dependent survival axis of M. tuberculosis . The FM which are characterized by the intracellular accumulation of lipid bodies (LBs), ensure a privileged existence for the bacilli through ready provision of nutrients and by conferring protection against bactericidal pathways. The mycobacterial secretory protein ESAT-6 has been identified as the molecular mediator of the FM differentiation process although little is known about the mechanism through which it induces this process. In the present study, we show that ESAT-6 induces GLUT-1 mediated enhanced glucose uptake by macrophages which is coupled to metabolic flux perturbations in the glycolytic pathway caused by differential rates of reaction at several steps in the pathway. Two major changes identified were the simultaneous buildup of DHAP (for Triglyceride synthesis) and AcCoA (for synthesis of 3-HB, ligand for the anti-lipolytic GPR109A). We also show that part of the observed effects involve protein- protein interactions between ESAT-6 and the macrophage glycolytic enzymes, Enolase1 and Phosphoglycerate kinase1.