Polar localization of virulence-related Esx-1 secretion in mycobacteria

• Published in: PLoS pathogens Vol. 5; no. 1; p. e1000285
• Main Authors: Carlsson, Fredric, Joshi, Shilpa A, Rangell, Linda, Brown, Eric J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.01.2009; Public Library of Science (PLoS)
• Subjects: 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase - metabolism; Actins; Animals; Antigens, Bacterial - genetics; Antigens, Bacterial - metabolism; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacteriology; Cell Biology/Cell Growth and Division; Cell Biology/Microbial Growth and Development; Cell Line; Cell Polarity; Cell Wall - metabolism; Experiments; Genetic aspects; Immunology/Cellular Microbiology and Pathogenesis; Infectious Diseases/Antimicrobials and Drug Resistance; Infectious Diseases/Bacterial Infections; Mice; Microbiology; Microbiology/Cellular Microbiology and Pathogenesis; Microbiology/Medical Microbiology; Microbiology/Microbial Evolution and Genomics; Microbiology/Microbial Physiology and Metabolism; Microscopy; Mutagenesis; Mycobacteria; Mycobacterial infections; Mycobacterium; Mycobacterium marinum - genetics; Mycobacterium marinum - metabolism; Peptidoglycan - metabolism; Physiological aspects; Proteins; Secretion; Virulence (Microbiology); Virulence Factors - genetics; Virulence Factors - metabolism; United States
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000285

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.