Tuesday, February 13, 2007

Tuberculosis Traffic Arrest

Mycobacterium tuberculosis is a life-threatening pathogen that persists in infected cells after being phagocytosed (eaten). Phagocytosed matter is usually digested but M. tuberculosis avoids this fate by blocking the acidification of the its compartment. The process can be studied in U937 cells because they behave like macrophages ("big eaters") and grow well in culture. Rab proteins form a large family of Ras-like GTPases that mediate vesicle trafficking, budding, etc. A recent report showed that Rab14 participates in trafficking to the early endosome, a stage just after the phagosome. Kyei and colleagues found that Rab14 associated with phagosomes containing live tuberculosis mycobacteria and investigated whether Rab14 was required for the arrested development of the phagosome. Phagosomes of U937 cells contain live tuberculosis bacilli of the strain H37Rv (green label, left panels). The middle panels show the same cells stained with a dye that detects endosomes that have undergone acidification, a step toward digestion and marker of the early endosome. A "knock-down" of Rab14 with siRNA permits the maturation of the phagosome, as demonstrated by the overlap of the acidified (red), bacillus-containing (green) phagosomes, (yellow color in the lower right panel). These findings suggest that inhibiting Rab14 may permit the infected cell to digest M. tuberculosis, thereby offering a new target for therapeutic intervention and potentially reducing the burden of this disease.
Kyei GB, Vergne I, Chua J, Roberts E, Harris J, Junutula JR, Deretic V. "Rab14 is critical for maintenance of Mycobacterium tuberculosis phagosome maturation arrest". EMBO J. 2006 Nov 15;25(22):5250-9.

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