ZFIN ID: ZDB-PUB-180418-73
Mycobacterial ESX-1 secretion system mediates host cell lysis through bacterium contact-dependent gross membrane disruptions
Conrad, W.H., Osman, M.M., Shanahan, J.K., Chu, F., Takaki, K.K., Cameron, J., Hopkinson-Woolley, D., Brosch, R., Ramakrishnan, L.
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
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.