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A mycobacterial encoded hypothetical protein is localized in mitochondria and regulates oxidative phosphorylation of infected macrophage

Rikesh Kumar Dubey, Ekta Dhamija, Alok K Mishra, Dheeraj Soam, Shivraj M Yabaji, Kanchan Srivastava, Kishore K Srivastava
European Respiratory Journal 2019 54: PA2961; DOI: 10.1183/13993003.congress-2019.PA2961
Rikesh Kumar Dubey
1CSIR-CENTRAL DRUG RESEARCH INSTITUTE, LUCKNOW, India
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  • For correspondence: rikesh.cdri@gmail.com
Ekta Dhamija
1CSIR-CENTRAL DRUG RESEARCH INSTITUTE, LUCKNOW, India
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Alok K Mishra
1CSIR-CENTRAL DRUG RESEARCH INSTITUTE, LUCKNOW, India
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Dheeraj Soam
1CSIR-CENTRAL DRUG RESEARCH INSTITUTE, LUCKNOW, India
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Shivraj M Yabaji
1CSIR-CENTRAL DRUG RESEARCH INSTITUTE, LUCKNOW, India
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Kanchan Srivastava
2KING GEORGE’S MEDICAL UNIVERSITY, LUCKNOW, India
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Kishore K Srivastava
1CSIR-CENTRAL DRUG RESEARCH INSTITUTE, LUCKNOW, India
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Abstract

Background: In the recent years mitochondria has emerged as one of the main target for Mycobacterium tuberculosis (Mtb) because of its multiple biological function. Herein we have investigated the Mtb proteins translocating to the mitochondria of the host macrophages.

Objective: The aim of the study was to identify the mycobacterial protein translocating to the mitochondria of the host macrophages after infection and its possible role in tuberculosis pathogenesis.

Methods: We confirmed the translocation of several mycobacterial proteins from cytosol to mitochondria using TB patient sera. 1D Nano LC MS/MS was employed further to identify the proteins in mitochondrial fractions. Identified protein, Rv0674 was cloned, purified and over expressed in Mycobacterium smegmatis (MSMEG). The role of this protein was evaluated for the growth, intracellular survival, mitochondrial membrane potential, apoptosis and ATP production.

Results and Conclusion: We identified a conserved hypothetical protein (Rv0674) from Mtb infected mitochondrial fractions of macrophages. The gene of this protein was decoded and characterized through a series of molecular approaches by recombinantly expressing it in MSMEG. The protein was found to be localized in the mitochondria of infected macrophages, in the macrophages of BAL fluid and drug resistant cases. Rv0674 plays significant roles in the apoptosis of infected macrophages, regulating mitochondrial proteins of the OXPHOS complexes which lead to ATP production and mitochondrial membrane potential. It is responsible for prolonging the growth of MSMEG and promoting its survival in infected macrophages

  • MDR-TB (multidrug-resistant tuberculosis)
  • Monocyte / Macrophage
  • Bronchoalveolar lavage

Footnotes

Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA2961.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2019
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A mycobacterial encoded hypothetical protein is localized in mitochondria and regulates oxidative phosphorylation of infected macrophage
Rikesh Kumar Dubey, Ekta Dhamija, Alok K Mishra, Dheeraj Soam, Shivraj M Yabaji, Kanchan Srivastava, Kishore K Srivastava
European Respiratory Journal Sep 2019, 54 (suppl 63) PA2961; DOI: 10.1183/13993003.congress-2019.PA2961

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A mycobacterial encoded hypothetical protein is localized in mitochondria and regulates oxidative phosphorylation of infected macrophage
Rikesh Kumar Dubey, Ekta Dhamija, Alok K Mishra, Dheeraj Soam, Shivraj M Yabaji, Kanchan Srivastava, Kishore K Srivastava
European Respiratory Journal Sep 2019, 54 (suppl 63) PA2961; DOI: 10.1183/13993003.congress-2019.PA2961
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