The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence.


Type
Article
Change log
Authors
Osman, Morwan M 
Shanahan, Jonathan K 
Chu, Frances 
Takaki, Kevin K 
Pinckert, Malte L 
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.

Description
Keywords
ESAT-6, ESX-1, phagosomal damage, virulence, Antigens, Bacterial, Bacterial Proteins, Humans, Mycobacterium marinum, Mycobacterium tuberculosis, Phagosomes, Protein Conformation, Tuberculoma, Type VII Secretion Systems, Virulence
Journal Title
Proc Natl Acad Sci U S A
Conference Name
Journal ISSN
0027-8424
1091-6490
Volume Title
119
Publisher
Proceedings of the National Academy of Sciences
Sponsorship
National Institutes of Health (NIH) (7R37A1054503-13)
Wellcome Trust (223103/Z/21/Z)