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

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Science  27 Mar 2009:
Vol. 323, Issue 5922, pp. 1729-1733
DOI: 10.1126/science.1169381

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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.

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