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Infection by tubercular mycobacteria is spread by nonlytic ejection from their amoeba hosts.

ABSTRACT: 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.

SUBMITTER: Hagedorn M

PROVIDER: S-EPMC2770343 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Infection by tubercular mycobacteria is spread by nonlytic ejection from their amoeba hosts.

Hagedorn Monica M Rohde Kyle H KH Russell David G DG Soldati Thierry T

Science (New York, N.Y.) 20090301 5922

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 ...[more]

PMID: 19325115

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Project description:BackgroundMost environmental non-tuberculous mycobacteria have been demonstrated to invade amoebal trophozoites and cysts, but such relationships are largely unknown for members of the Mycobacterium tuberculosis complex. An environmental source has been proposed for the animal Mycobacterium bovis and the human Mycobacterium canettii.Methodology/principal findingsUsing optic and electron microscopy and co-culture methods, we observed that 89±0.6% of M. canettii, 12.4±0.3% of M. tuberculosis, 11.7±2% of M. bovis and 11.2±0.5% of Mycobacterium avium control organisms were phagocytized by Acanthamoeba polyphaga, a ratio significantly higher for M. canettii (P = 0.03), correlating with the significantly larger size of M. canetti organisms (P = 0.035). The percentage of intraamoebal mycobacteria surviving into cytoplasmic vacuoles was 32±2% for M. canettii, 26±1% for M. tuberculosis, 28±2% for M. bovis and 36±2% for M. avium (P = 0.57). M. tuberculosis, M. bovis and M. avium mycobacteria were further entrapped within the double wall of <1% amoebal cysts, but no M. canettii organisms were observed in amoebal cysts. The number of intracystic mycobacteria was significantly (P = 10(-6)) higher for M. avium than for the M. tuberculosis complex, and sub-culturing intracystic mycobacteria yielded significantly more (P = 0.02) M. avium organisms (34×10(4) CFU/mL) than M. tuberculosis (42×10(1) CFU/mL) and M. bovis (35×10(1) CFU/mL) in the presence of a washing fluid free of mycobacteria. Mycobacteria survived in the cysts for up to 18 days and cysts protected M. tuberculosis organisms against mycobactericidal 5 mg/mL streptomycin and 2.5% glutaraldehyde.Conclusions/significanceThese data indicate that M. tuberculosis complex organisms are amoeba-resistant organisms, as previously demonstrated for non-tuberculous, environmental mycobacteria. Intercystic survival of tuberculous mycobacteria, except for M. canettii, protect them against biocides and could play a role in their life cycle.

Dataset Information

Infection by tubercular mycobacteria is spread by nonlytic ejection from their amoeba hosts.

Publications

Infection by tubercular mycobacteria is spread by nonlytic ejection from their amoeba hosts.

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