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Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages

Mycobacterium tuberculosis (Mtb) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a Mtb acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress respon...

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Autores principales: Behera, Ananyaashree, Jain, Preeti, Ganguli, Geetanjali, Biswas, Mainak, Padhi, Avinash, Pattanaik, Kali Prasad, Nayak, Barsa, Ergün, Süleyman, Hagens, Kristine, Redinger, Natalja, Saqib, Mohd, Mishra, Bibhuti B., Schaible, Ulrich E., Karnati, Srikanth, Sonawane, Avinash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909987/
https://www.ncbi.nlm.nih.gov/pubmed/35269727
http://dx.doi.org/10.3390/ijms23052584
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author Behera, Ananyaashree
Jain, Preeti
Ganguli, Geetanjali
Biswas, Mainak
Padhi, Avinash
Pattanaik, Kali Prasad
Nayak, Barsa
Ergün, Süleyman
Hagens, Kristine
Redinger, Natalja
Saqib, Mohd
Mishra, Bibhuti B.
Schaible, Ulrich E.
Karnati, Srikanth
Sonawane, Avinash
author_facet Behera, Ananyaashree
Jain, Preeti
Ganguli, Geetanjali
Biswas, Mainak
Padhi, Avinash
Pattanaik, Kali Prasad
Nayak, Barsa
Ergün, Süleyman
Hagens, Kristine
Redinger, Natalja
Saqib, Mohd
Mishra, Bibhuti B.
Schaible, Ulrich E.
Karnati, Srikanth
Sonawane, Avinash
author_sort Behera, Ananyaashree
collection PubMed
description Mycobacterium tuberculosis (Mtb) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a Mtb acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress responses by inducing peroxisome formation. An inducible Rv3034c deletion mutant of Mtb failed to induce peroxisome biogenesis, expression of the peroxisomal β-oxidation pathway intermediates (ACOX1, ACAA1, MFP2) in macrophages, resulting in reduced intracellular survival compared to the parental strain. This reduced virulence phenotype was rescued by repletion of Rv3034c. Peroxisome induction depended on the interaction between Rv3034c and the macrophage mannose receptor (MR). Interaction between Rv3034c and MR induced expression of the peroxisomal biogenesis proteins PEX5p, PEX13p, PEX14p, PEX11β, PEX19p, the peroxisomal membrane lipid transporter ABCD3, and catalase. Expression of PEX14p and ABCD3 was also enhanced in lungs from Mtb aerosol-infected mice. This is the first report that peroxisome-mediated control of ROS balance is essential for innate immune responses to Mtb but can be counteracted by the mycobacterial acetyltransferase Rv3034c. Thus, peroxisomes represent interesting targets for host-directed therapeutics to tuberculosis.
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spelling pubmed-89099872022-03-11 Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages Behera, Ananyaashree Jain, Preeti Ganguli, Geetanjali Biswas, Mainak Padhi, Avinash Pattanaik, Kali Prasad Nayak, Barsa Ergün, Süleyman Hagens, Kristine Redinger, Natalja Saqib, Mohd Mishra, Bibhuti B. Schaible, Ulrich E. Karnati, Srikanth Sonawane, Avinash Int J Mol Sci Article Mycobacterium tuberculosis (Mtb) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a Mtb acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress responses by inducing peroxisome formation. An inducible Rv3034c deletion mutant of Mtb failed to induce peroxisome biogenesis, expression of the peroxisomal β-oxidation pathway intermediates (ACOX1, ACAA1, MFP2) in macrophages, resulting in reduced intracellular survival compared to the parental strain. This reduced virulence phenotype was rescued by repletion of Rv3034c. Peroxisome induction depended on the interaction between Rv3034c and the macrophage mannose receptor (MR). Interaction between Rv3034c and MR induced expression of the peroxisomal biogenesis proteins PEX5p, PEX13p, PEX14p, PEX11β, PEX19p, the peroxisomal membrane lipid transporter ABCD3, and catalase. Expression of PEX14p and ABCD3 was also enhanced in lungs from Mtb aerosol-infected mice. This is the first report that peroxisome-mediated control of ROS balance is essential for innate immune responses to Mtb but can be counteracted by the mycobacterial acetyltransferase Rv3034c. Thus, peroxisomes represent interesting targets for host-directed therapeutics to tuberculosis. MDPI 2022-02-26 /pmc/articles/PMC8909987/ /pubmed/35269727 http://dx.doi.org/10.3390/ijms23052584 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Behera, Ananyaashree
Jain, Preeti
Ganguli, Geetanjali
Biswas, Mainak
Padhi, Avinash
Pattanaik, Kali Prasad
Nayak, Barsa
Ergün, Süleyman
Hagens, Kristine
Redinger, Natalja
Saqib, Mohd
Mishra, Bibhuti B.
Schaible, Ulrich E.
Karnati, Srikanth
Sonawane, Avinash
Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages
title Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages
title_full Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages
title_fullStr Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages
title_full_unstemmed Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages
title_short Mycobacterium tuberculosis Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages
title_sort mycobacterium tuberculosis acetyltransferase suppresses oxidative stress by inducing peroxisome formation in macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909987/
https://www.ncbi.nlm.nih.gov/pubmed/35269727
http://dx.doi.org/10.3390/ijms23052584
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