Mycobacterium tuberculosis Calcium Pump CtpF Modulates the Autophagosome in an mTOR-Dependent Manner
| Autor: | Salik Miskat Borbora, Harsh Bansia, Rajni Garg, Prakruti R Singh, Kithiganahalli Narayanaswamy Balaji, Valakunja Nagaraja, Sandhya Rao, Rinkee Verma |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Autophagosome autophagy CtpF Calcium pump 030106 microbiology Immunology lcsh:QR1-502 chemistry.chemical_element Calcium Microbiology lcsh:Microbiology 03 medical and health sciences Cellular and Infection Microbiology Downregulation and upregulation PI3K/AKT/mTOR pathway Cellular compartment Original Research calcium Autophagy Mycobacterium tuberculosis Cell biology 030104 developmental biology Infectious Diseases chemistry tuberculosis Second messenger system mTOR |
| Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, Vol 10 (2020) |
| ISSN: | 2235-2988 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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