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Science 27 March 2009:
Vol. 323. no. 5922, pp. 1729 - 1733
DOI: 10.1126/science.1169381

Reports

Infection by Tubercular Mycobacteria Is Spread by Nonlytic Ejection from Their Amoeba Hosts

Monica Hagedorn,1 Kyle H. Rohde,2 David G. Russell,2 Thierry Soldati1*

To generate efficient vaccines and cures for Mycobacterium tuberculosis, we need a far better understanding of its modes of infection, persistence, and spreading. Host cell entry and the establishment of a replication niche are well understood, but little is known about how tubercular mycobacteria exit host cells and disseminate the infection. Using the social amoeba Dictyostelium as a genetically tractable host for pathogenic mycobacteria, we discovered that M. tuberculosis and M. marinum, but not M. avium, are ejected from the cell through an actin-based structure, the ejectosome. This conserved nonlytic spreading mechanism requires a cytoskeleton regulator from the host and an intact mycobacterial ESX-1 secretion system. This insight offers new directions for research into the spreading of tubercular mycobacteria infections in mammalian cells.

1 Département de Biochimie, Faculté des Sciences, Université de Genève, Sciences II, 30 quai Ernest Ansermet, CH-1211 Genève-4, Switzerland.
2 Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

* To whom correspondence should be addressed. E-mail: thierry.soldati{at}unige.ch

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Characterization of a Mycobacterium tuberculosis ESX-3 Conditional Mutant: Essentiality and Rescue by Iron and Zinc.
A. Serafini, F. Boldrin, G. Palu, and R. Manganelli (2009)
J. Bacteriol. 191, 6340-6344
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