<i>Mycobacterium tuberculosis</i> Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages
<i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a <i>Mtb</i> acetyltransferase (Rv3034c) as a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/5/2584 |
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| author | Ananyaashree Behera Preeti Jain Geetanjali Ganguli Mainak Biswas Avinash Padhi Kali Prasad Pattanaik Barsa Nayak Süleyman Ergün Kristine Hagens Natalja Redinger Mohd Saqib Bibhuti B. Mishra Ulrich E. Schaible Srikanth Karnati Avinash Sonawane |
| author_facet | Ananyaashree Behera Preeti Jain Geetanjali Ganguli Mainak Biswas Avinash Padhi Kali Prasad Pattanaik Barsa Nayak Süleyman Ergün Kristine Hagens Natalja Redinger Mohd Saqib Bibhuti B. Mishra Ulrich E. Schaible Srikanth Karnati Avinash Sonawane |
| author_sort | Ananyaashree Behera |
| collection | DOAJ |
| description | <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a <i>Mtb</i> acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress responses by inducing peroxisome formation. An inducible <i>Rv3034c</i> deletion mutant of <i>Mtb</i> 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 <i>Rv3034c</i>. 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 <i>Mtb</i> aerosol-infected mice. This is the first report that peroxisome-mediated control of ROS balance is essential for innate immune responses to <i>Mtb</i> but can be counteracted by the mycobacterial acetyltransferase <i>Rv3034c</i>. Thus, peroxisomes represent interesting targets for host-directed therapeutics to tuberculosis. |
| first_indexed | 2024-03-09T20:38:19Z |
| format | Article |
| id | doaj.art-d389b37abd3144c2beed7dfa1b98f944 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:38:19Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d389b37abd3144c2beed7dfa1b98f9442023-11-23T23:06:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235258410.3390/ijms23052584<i>Mycobacterium tuberculosis</i> Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in MacrophagesAnanyaashree Behera0Preeti Jain1Geetanjali Ganguli2Mainak Biswas3Avinash Padhi4Kali Prasad Pattanaik5Barsa Nayak6Süleyman Ergün7Kristine Hagens8Natalja Redinger9Mohd Saqib10Bibhuti B. Mishra11Ulrich E. Schaible12Srikanth Karnati13Avinash Sonawane14School of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, IndiaNational Institute of Immunology, New Delhi 110067, IndiaSchool of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, IndiaSchool of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, IndiaSchool of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, IndiaSchool of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, IndiaDepartment of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore 453552, IndiaInstitute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, 97070 Würzburg, GermanyDepartment of Cellular Microbiology, Program Area Infections, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, GermanyDepartment of Cellular Microbiology, Program Area Infections, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, GermanyDepartment of Immunology and Microbial Disease, Albany Medical College, NY 12208, USADepartment of Immunology and Microbial Disease, Albany Medical College, NY 12208, USADepartment of Cellular Microbiology, Program Area Infections, Research Center Borstel-Leibniz Lung Center, 23845 Borstel, GermanyInstitute of Anatomy and Cell Biology, Julius-Maximilians-University Würzburg, 97070 Würzburg, GermanySchool of Biotechnology, KIIT Deemed to be University, Bhubaneswar 751024, India<i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a <i>Mtb</i> acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress responses by inducing peroxisome formation. An inducible <i>Rv3034c</i> deletion mutant of <i>Mtb</i> 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 <i>Rv3034c</i>. 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 <i>Mtb</i> aerosol-infected mice. This is the first report that peroxisome-mediated control of ROS balance is essential for innate immune responses to <i>Mtb</i> but can be counteracted by the mycobacterial acetyltransferase <i>Rv3034c</i>. Thus, peroxisomes represent interesting targets for host-directed therapeutics to tuberculosis.https://www.mdpi.com/1422-0067/23/5/2584peroxisome<i>Mycobacterium tuberculosis</i>Rv3034cacetyltransferasemacrophagesoxidative stress |
| spellingShingle | Ananyaashree Behera Preeti Jain Geetanjali Ganguli Mainak Biswas Avinash Padhi Kali Prasad Pattanaik Barsa Nayak Süleyman Ergün Kristine Hagens Natalja Redinger Mohd Saqib Bibhuti B. Mishra Ulrich E. Schaible Srikanth Karnati Avinash Sonawane <i>Mycobacterium tuberculosis</i> Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages International Journal of Molecular Sciences peroxisome <i>Mycobacterium tuberculosis</i> Rv3034c acetyltransferase macrophages oxidative stress |
| title | <i>Mycobacterium tuberculosis</i> Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages |
| title_full | <i>Mycobacterium tuberculosis</i> Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages |
| title_fullStr | <i>Mycobacterium tuberculosis</i> Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages |
| title_full_unstemmed | <i>Mycobacterium tuberculosis</i> Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages |
| title_short | <i>Mycobacterium tuberculosis</i> Acetyltransferase Suppresses Oxidative Stress by Inducing Peroxisome Formation in Macrophages |
| title_sort | i mycobacterium tuberculosis i acetyltransferase suppresses oxidative stress by inducing peroxisome formation in macrophages |
| topic | peroxisome <i>Mycobacterium tuberculosis</i> Rv3034c acetyltransferase macrophages oxidative stress |
| url | https://www.mdpi.com/1422-0067/23/5/2584 |
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