The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence.
Osman, Morwan M
Shanahan, Jonathan K
Takaki, Kevin K
Pinckert, Malte L
Proceedings of the National Academy of Sciences of the United States of America
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Osman, M. M., Shanahan, J. K., Chu, F., Takaki, K. K., Pinckert, M. L., Pagán, A. J., Brosch, R., et al. (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, 119 (11) https://doi.org/10.1073/pnas.2122161119
SignificanceTuberculosis (TB), an ancient disease of humanity, continues to be a major cause of worldwide death. The causative agent of TB, <i>Mycobacterium tuberculosis</i>, and its close pathogenic relative <i>Mycobacterium marinum</i>, 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.
Virulence, ESAT-6, Esx-1, Phagosomal Damage
HHS | NIH | National Institute of Allergy and Infectious Diseases (R37 AI054503)
Wellcome Trust (223103/Z/21/Z)
External DOI: https://doi.org/10.1073/pnas.2122161119
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335970
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/