The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence
Morwan M. Osman, Jonathan K. Shanahan, Frances Chu, Kevin K. Takaki, Malte L. Pinckert, Antonio J. Pagán, Roland Brosch, William H. Conrad, et al. (9 authors)
Proceedings of the National Academy of Sciences · 2022-03
Abstract
Significance Tuberculosis (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.
MeSH terms
- Virulence
- Phagosome
- Mycobacterium marinum
- Microbiology
- ESAT-6
- Secretion
- Mycobacterium tuberculosis
- Macrophage
- Mycobacterium
- Biology
- Tuberculosis
- Phagocytosis