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A transparent zebrafish infected with tuberculosis.
For the first time, researchers have produced images of tuberculosis inside a living organism. This achievement could boost understanding of this infectious disease and how it develops in the human body.
Dr. Lalita Ramakrishnan, assistant professor of microbiology at UW, along with microbiologist Dr. Muse Davis and molecular and cellular biologist Dr. Hilary Clay, were able to obtain the images while examing a zebrafish embryo. Their images, published in the cover article of the December 2002 issue of Immunity, depicted Mycobacterium marinum in the developing fish embryo. M. marinum causes TB in zebrafish and is a close genetic relative of M. tuberculosis, the bacterium that infects humans.
The optically transparent zebrafish embryos allowed the UW researchers to visualize bodily processes in conjunction with direct imaging of labeled bacteria. These images give clues to how tuberculosis granulomas might form in humans.
TB infects an estimated one-third of the world's population, but in most cases the infected individuals are asymptomatic, and cannot spread the disease. The bacteria reside within granulomas, which are complex structures composed of various immune cells. Infected individuals are at risk to develop active TB, which is harmful to them and contagious to others.
Ramakrishnan's laboratory is interested in the factors contributing to granuloma formation and how those factors determine whether a person who is exposed to tubercle bacilli clears the infection immediately, acquires an asymptomatic infection by containing the infection in granulomas, or develops a progressive disseminated disease.
To study the contribution of host factors to tuberculosis outcomes, Davis and his colleagues study the zebrafish as a model host. Apart from being optically transparent, the zebrafish is a natural host for TB that is genetically tractable. It is the only vertebrate host that is amenable to forward genetic screens. These screens identify host response elements. In addition, the function of individual host response genes can be abrogates using anti-sense RNAs. This characteristic permits the study of the role of individual immune effector molecules in tuberculosis.
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