Polar localization of virulence-related Esx-1 secretion in mycobacteria.
The Esx-1 (type VII) secretion system is critical for virulence of both Mycobacterium tuberculosis and Mycobacterium marinum, and is highly conserved between the two species. Despite its importance, there has been no direct visualization of Esx-1 secretion until now. In M. marinum, we show that secretion of Mh3864, a novel Esx-1 substrate that remains partially cell wall-associated after translocation, occurred in polar regions, indicating that Esx-1 secretion takes place in these regions. Analysis of Esx-1 secretion in infected host cells suggested that Esx-1 activity is similarly localized in vivo. A core component of the Esx-1 apparatus, Mh3870, also localized to bacterial poles, showing a preference for new poles with active cell wall peptidoglycan (PGN) synthesis. This work demonstrates that the Esx-1 secretion machine localizes to, and is active at, the bacterial poles. Thus, virulence-related protein secretion is localized in mycobacteria, suggesting new potential therapeutic targets, which are urgently needed.
Carlsson
Fredric
F
Department of Microbial Pathogenesis, Genentech Inc, South San Francisco, California, United States of America. carlsson.fredric@gene.com
Joshi
Shilpa A
SA
Rangell
Linda
L
Brown
Eric J
EJ
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000378:metabolism; D000199:Actins; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity; D002473:Cell Wall / Q000378:metabolism; D051379:Mice; D016296:Mutagenesis; D019910:Mycobacterium marinum / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D010457:Peptidoglycan; D037521:Virulence Factors; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase