The C terminus of the mycobacterium ESX-1 secretion system substrate ESAT-6 is required for phagosomal membrane damage and virulence.
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Authors
Osman, Morwan M
Shanahan, Jonathan K
Chu, Frances
Takaki, Kevin K
Pinckert, Malte L
Publication Date
2022-03-10Journal Title
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424
Volume
119
Issue
11
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
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
Abstract
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.
Keywords
Virulence, ESAT-6, Esx-1, Phagosomal Damage
Sponsorship
HHS | NIH | National Institute of Allergy and Infectious Diseases (R37 AI054503)
Wellcome Trust (223103/Z/21/Z)
Identifiers
35271388, PMC8931374
External DOI: https://doi.org/10.1073/pnas.2122161119
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335970
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