Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 6, Pages 1371-1376Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1620133114
Keywords
Mycobacterium tuberculosis; Mycobacterium marinum; ESAT-6; ESX-1 secretion system; cell membrane lysis
Categories
Funding
- Wellcome Trust
- National Institutes of Health (NIH) [R37AI054503]
- National Institute of Health Research Cambridge Biomedical Research Centre
- National Science Foundation [DGE-1256082]
- NIH [T32 AI55396]
- Agence National de Recherche [ANR-14-JAMR-001-02, ANR-10-LABX-62-IBEID]
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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.
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