Osman, Morwan M, Shanahan, Jonathan K, Chu, Frances et al. (6 more authors) (2022) The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence. Proceedings of the National Academy of Sciences of the United States of America. e2122161119. ISSN 1091-6490
Abstract
SignificanceTuberculosis (TB), an ancient disease of humanity, continues to be a major cause of worldwide death. The causative agent of TB, Mycobacterium tuberculosis, and its close pathogenic relative Mycobacterium marinum, initially infect, evade, and exploit macrophages, a major host defense against invading pathogens. Within macrophages, mycobacteria reside within host membrane-bound compartments called phagosomes. Mycobacterium-induced damage of the phagosomal membranes is integral to pathogenesis, and this activity has been attributed to the specialized mycobacterial secretion system ESX-1, and particularly to ESAT-6, its major secreted protein. Here, we show that the integrity of the unstructured ESAT-6 C terminus is required for macrophage phagosomal damage, granuloma formation, and virulence.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Keywords: | Antigens, Bacterial/chemistry,Bacterial Proteins/chemistry,Humans,Mycobacterium marinum/metabolism,Mycobacterium tuberculosis/metabolism,Phagosomes/metabolism,Protein Conformation,Tuberculoma/microbiology,Type VII Secretion Systems/metabolism,Virulence |
Dates: |
|
Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Chemistry (York) |
Depositing User: | Pure (York) |
Date Deposited: | 03 Sep 2024 14:00 |
Last Modified: | 16 Oct 2024 20:07 |
Published Version: | https://doi.org/10.1073/pnas.2122161119 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1073/pnas.2122161119 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:216798 |
Download
Description: osman-et-al-2022-the-c-terminus-of-the-mycobacterium-esx-1-secretion-system-substrate-esat-6-is-required-for-phagosomal
Licence: CC-BY 2.5