Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes
Mycobacterium tuberculosis (Mtb) inhibits autophagy to promote its survival in host cells. However, the molecular mechanisms by which Mtb inhibits autophagy are poorly understood. Here, we report a previously unknown mechanism in which Mtb phosphoribosyltransferase (MtbPRT) inhibits autophagy in an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.676456/full |
| _version_ | 1818640743098482688 |
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| author | Srabasti Sengupta Barsa Nayak Michael Meuli Peter Sander Peter Sander Snehasish Mishra Avinash Sonawane |
| author_facet | Srabasti Sengupta Barsa Nayak Michael Meuli Peter Sander Peter Sander Snehasish Mishra Avinash Sonawane |
| author_sort | Srabasti Sengupta |
| collection | DOAJ |
| description | Mycobacterium tuberculosis (Mtb) inhibits autophagy to promote its survival in host cells. However, the molecular mechanisms by which Mtb inhibits autophagy are poorly understood. Here, we report a previously unknown mechanism in which Mtb phosphoribosyltransferase (MtbPRT) inhibits autophagy in an mTOR, negative regulator of autophagy, independent manner by inducing histone hypermethylation (H3K9me2/3) at the Atg5 and Atg7 promoters by activating p38-MAPK- and EHMT2 methyltransferase-dependent signaling pathways. Additionally, we find that MtbPRT induces EZH2 methyltransferase-dependent H3K27me3 hypermethylation and reduces histone acetylation modifications (H3K9ac and H3K27ac) by upregulating histone deacetylase 3 to inhibit autophagy. In summary, this is the first demonstration that Mtb inhibits autophagy by inducing histone hypermethylation in autophagy-related genes to promote intracellular bacterial survival. |
| first_indexed | 2024-12-16T23:16:07Z |
| format | Article |
| id | doaj.art-daa45af2b27b48639bb068b41851d0bf |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-16T23:16:07Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-daa45af2b27b48639bb068b41851d0bf2022-12-21T22:12:17ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-07-011110.3389/fcimb.2021.676456676456Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related GenesSrabasti Sengupta0Barsa Nayak1Michael Meuli2Peter Sander3Peter Sander4Snehasish Mishra5Avinash Sonawane6School of Biotechnology, KIIT Deemed to be University, Bhubaneswar, IndiaDepartment of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, IndiaInstitut für Medizinische Mikrobiologie, Universität Zürich, Zurich, SwitzerlandInstitut für Medizinische Mikrobiologie, Universität Zürich, Zurich, SwitzerlandNationales Zentrum für Mykobakterien, Zürich, SwitzerlandSchool of Biotechnology, KIIT Deemed to be University, Bhubaneswar, IndiaDepartment of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, IndiaMycobacterium tuberculosis (Mtb) inhibits autophagy to promote its survival in host cells. However, the molecular mechanisms by which Mtb inhibits autophagy are poorly understood. Here, we report a previously unknown mechanism in which Mtb phosphoribosyltransferase (MtbPRT) inhibits autophagy in an mTOR, negative regulator of autophagy, independent manner by inducing histone hypermethylation (H3K9me2/3) at the Atg5 and Atg7 promoters by activating p38-MAPK- and EHMT2 methyltransferase-dependent signaling pathways. Additionally, we find that MtbPRT induces EZH2 methyltransferase-dependent H3K27me3 hypermethylation and reduces histone acetylation modifications (H3K9ac and H3K27ac) by upregulating histone deacetylase 3 to inhibit autophagy. In summary, this is the first demonstration that Mtb inhibits autophagy by inducing histone hypermethylation in autophagy-related genes to promote intracellular bacterial survival.https://www.frontiersin.org/articles/10.3389/fcimb.2021.676456/fullTuberculosisMycobacterium tuberculosisAutophagyHistone hypermethylationMAPK pathwayepigenetic modification |
| spellingShingle | Srabasti Sengupta Barsa Nayak Michael Meuli Peter Sander Peter Sander Snehasish Mishra Avinash Sonawane Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes Frontiers in Cellular and Infection Microbiology Tuberculosis Mycobacterium tuberculosis Autophagy Histone hypermethylation MAPK pathway epigenetic modification |
| title | Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes |
| title_full | Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes |
| title_fullStr | Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes |
| title_full_unstemmed | Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes |
| title_short | Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes |
| title_sort | mycobacterium tuberculosis phosphoribosyltransferase promotes bacterial survival in macrophages by inducing histone hypermethylation in autophagy related genes |
| topic | Tuberculosis Mycobacterium tuberculosis Autophagy Histone hypermethylation MAPK pathway epigenetic modification |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2021.676456/full |
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