Mycobacterium tuberculosis Calcium Pump CtpF Modulates the Autophagosome in an mTOR-Dependent Manner

Garg, R and Borbora, SM and Bansia, H and Rao, S and Singh, P and Verma, R and Balaji, KN and Nagaraja, V (2020) Mycobacterium tuberculosis Calcium Pump CtpF Modulates the Autophagosome in an mTOR-Dependent Manner. In: Frontiers in Cellular and Infection Microbiology, 10 .

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Abstract

Calcium is a very important second messenger, whose concentration in various cellular compartments is under tight regulation. A disturbance in the levels of calcium in these compartments can play havoc in the cell, as it regulates various cellular processes by direct or indirect mechanisms. Here, we have investigated the functional importance of a calcium transporting P2A ATPase, CtpF of Mycobacterium tuberculosis (Mtb) in the pathogen's interaction with the host. Among its uncanny ways of dealing with the host with umpteen strategies for survival and persistence in humans, CtpF is identified as a new player. The levels of ctpF are upregulated in macrophage stresses like hypoxia, high nitric oxide levels and acidic pH. Using confocal microscopy and fluorimetry, we show that CtpF effluxes calcium in macrophages in early stages of Mtb infection. Downregulation of ctpF expression by conditional knockdown resulted in perturbation of host calcium levels and consequent decreased activation of mTOR. We present a mechanism how calcium efflux by the pathogen inhibits mTOR-dependent autophagy and enhances bacterial survival. Our work highlights how Mtb engages its metal efflux pumps to exploit host autophagic process for its proliferation. © Copyright © 2020 Garg, Borbora, Bansia, Rao, Singh, Verma, Balaji and Nagaraja.

Item Type:	Journal Article
Publication:	Frontiers in Cellular and Infection Microbiology
Publisher:	Frontiers Media S.A
Additional Information:	copyright to this article belongs to Frontiers Media S.A
Keywords:	adenosine triphosphatase (calcium); adenosine triphosphatase (potassium sodium); calcium; gentamicin; long untranslated RNA; mammalian target of rapamycin; messenger RNA; microRNA 1; RNA 16S; small interfering RNA; vanadate sodium; von Willebrand factor, 3' untranslated region; angiogenesis; Article; autophagosome; bacterial growth; bacterial strain; bacterial survival; biofilm; bioinformatics; calcium transport; cell isolation; cell migration assay; cell motility; cell proliferation; cell survival; CFU counting; confocal microscopy; CRISPR-CAS9 system; dental pellicle; down regulation; endothelium cell; enzyme activity; fluorometry; gene expression; genetic transfection; immunoblotting; infection; macrophage; macrophage infection; maximum inhibition; membrane vesicle; mineral supplementation; mycobacterial growth; Mycobacterium smegmatis; Mycobacterium tuberculosis; protein expression; protein phosphorylation; real time polymerase chain reaction; RNA extraction; RNA interference; sequence alignment; sequence homology; signal transduction; THP-1 cell line; upregulation; xenophagy
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	19 Nov 2020 11:38
Last Modified:	19 Nov 2020 11:38
URI:	http://eprints.iisc.ac.in/id/eprint/66909

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