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http://hdl.handle.net/2080/2819
Title: | Calcimycin mediates mycobacterial killing by inducing intracellular calcium-regulated autophagy in a P2RX7 dependent manner |
Authors: | Mawatwal, Shradha Behura, Assirbad Ghosh, Abhirupa Mishra, Abtar Kidwai, Saqib Saha, Sudipto Singh, Ramandeep Dhiman, Rohan |
Keywords: | Autophagy Calcimycin Intracellular mycobacteria THP-1 cells |
Issue Date: | Dec-2017 |
Citation: | EMBO-India Symposium “Autophagy: Cellular mechanisms and significance in health and disease", Bhubaneswar, Odisha, India, 11 – 13 December, 2017 |
Abstract: | AIM - To understand the mechanism of autophagy induction by calcimycin and its effect on the viability of intracellular mycobacteria in THP-1 cells. RESULT - We noticed that treatment with calcimycin led to up-regulation of different autophagy markers like Beclin-1, autophagy-related gene (Atg) 7, Atg 3 and enhanced microtubule-associated protein 1A/1B-light chain 3-I (LC3-I) to LC3-II conversion in macrophages. This calcimycin-mediated killing of intracellular M. smegmatis and M. bovis BCG was abrogated in the presence of 3-methyladenine (3-MA). We also demonstrate that calcimycin binding with purinergic receptor P2X7 (P2RX7) led to increase in intracellular calcium level that regulates the extracellular release of ATP. ATP was able to regulate calcimycin-induced autophagy through P2RX7 in an autocrine fashion. Blocking of either P2RX7 expression by 1-[N,O-bis(5-Isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) or reducing intracellular calcium levels by 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra (acetoxy-methyl) ester (BAPTA-AM) abrogated the antimycobacterial activity of calcimycin. Taken together, these results showed that calcimycin exerts its antimycobacterial effect by regulating intracellular calcium-dependent ATP release that induces autophagy in a P2RX7 dependent manner. CONCLUSION - Calcimycin exerts its antimycobacterial effect by regulating intracellular calcium-dependent ATP release that induces autophagy in a P2RX7 dependent manner. SIGNIFICANCE - Understanding the mechanism of autophagy by calcimycin may provide an attractive target for the control of mycobacterial infection, which will help in developing better therapeutic interventions against TB. |
Description: | Copyright of this document belongs to proceedings publisher. |
URI: | http://hdl.handle.net/2080/2819 |
Appears in Collections: | Conference Papers |
Files in This Item:
File | Description | Size | Format | |
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2017_EMBO-India_RDhiman_Calcimycin.pdf | Poster Presentation | 2.74 MB | Adobe PDF | View/Open |
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