PUBLICATION
Mycobacterial ESX-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions
- Authors
- Conrad, W.H., Osman, M.M., Shanahan, J.K., Chu, F., Takaki, K.K., Cameron, J., Hopkinson-Woolley, D., Brosch, R., Ramakrishnan, L.
- ID
- ZDB-PUB-180418-73
- Date
- 2017
- Source
- Proceedings of the National Academy of Sciences of the United States of America 114: 1371-1376 (Journal)
- Registered Authors
- Cameron, James, Chu, Frances, Ramakrishnan, Lalita, Takaki, Kevin
- Keywords
- ESAT-6, ESX-1 secretion system, Mycobacterium marinum, Mycobacterium tuberculosis, cell membrane lysis
- MeSH Terms
-
- Animals
- Antigens, Bacterial/genetics
- Antigens, Bacterial/metabolism*
- Bacterial Adhesion
- Bacterial Proteins/genetics
- Bacterial Proteins/metabolism*
- Bacterial Secretion Systems/genetics
- Bacterial Secretion Systems/metabolism
- Cell Line
- Cell Line, Tumor
- Erythrocyte Membrane/metabolism*
- Erythrocyte Membrane/microbiology
- Erythrocytes/metabolism*
- Erythrocytes/microbiology
- Hemolysis*
- Host-Pathogen Interactions
- Humans
- Larva/metabolism
- Larva/microbiology
- Macrophages/metabolism
- Macrophages/microbiology
- Mice
- Mycobacterium marinum/genetics
- Mycobacterium marinum/metabolism
- Mycobacterium marinum/pathogenicity
- Mycobacterium tuberculosis/genetics
- Mycobacterium tuberculosis/metabolism
- Mycobacterium tuberculosis/pathogenicity
- Sheep
- Virulence
- Zebrafish
- PubMed
- 28119503 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Conrad, W.H., Osman, M.M., Shanahan, J.K., Chu, F., Takaki, K.K., Cameron, J., Hopkinson-Woolley, D., Brosch, R., Ramakrishnan, L. (2017) Mycobacterial ESX-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions. Proceedings of the National Academy of Sciences of the United States of America. 114:1371-1376.
Abstract
Mycobacterium tuberculosis and Mycobacterium marinum are thought to exert virulence, in part, through their ability to lyse host cell membranes. The type VII secretion system ESX-1 [6-kDa early secretory antigenic target (ESAT-6) secretion system 1] is required for both virulence and host cell membrane lysis. Both activities are attributed to the pore-forming activity of the ESX-1-secreted substrate ESAT-6 because multiple studies have reported that recombinant ESAT-6 lyses eukaryotic membranes. We too find ESX-1 of M. tuberculosis and M. marinum lyses host cell membranes. However, we find that recombinant ESAT-6 does not lyse cell membranes. The lytic activity previously attributed to ESAT-6 is due to residual detergent in the preparations. We report here that ESX-1-dependent cell membrane lysis is contact dependent and accompanied by gross membrane disruptions rather than discrete pores. ESX-1-mediated lysis is also morphologically distinct from the contact-dependent lysis of other bacterial secretion systems. Our findings suggest redirection of research to understand the mechanism of ESX-1-mediated lysis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping