Header

UZH-Logo

Maintenance Infos

Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes


Sengupta, Srabasti; Nayak, Barsa; Meuli, Michael; Sander, Peter; Mishra, Snehasish; Sonawane, Avinash (2021). Mycobacterium tuberculosis Phosphoribosyltransferase Promotes Bacterial Survival in Macrophages by Inducing Histone Hypermethylation in Autophagy-Related Genes. Frontiers in Cellular and Infection Microbiology, 11:676456.

Abstract

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.

Keywords: Autophagy; Histone hypermethylation; MAPK pathway; Mycobacterium tuberculosis; Tuberculosis; epigenetic modification.

Abstract

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.

Keywords: Autophagy; Histone hypermethylation; MAPK pathway; Mycobacterium tuberculosis; Tuberculosis; epigenetic modification.

Statistics

Citations

Dimensions.ai Metrics
5 citations in Web of Science®
8 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

20 downloads since deposited on 21 Oct 2021
7 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Microbiology
Life Sciences > Immunology
Health Sciences > Microbiology (medical)
Health Sciences > Infectious Diseases
Language:English
Date:July 2021
Deposited On:21 Oct 2021 15:44
Last Modified:25 Jun 2024 01:45
Publisher:Frontiers Research Foundation
ISSN:2235-2988
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fcimb.2021.676456
PubMed ID:34381738
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)