New Scholar Award in Global Infectious Disease
Anita Sil, M.D., Ph.D
University of California - San Francisco

Molecular Analysis of Detoxification of Nitric Oxide in Histoplasma capsulatum

My laboratory studies the pathogen Histoplasma capsulatum, thought to be the most common cause of fungal respiratory infections in the world. H. capsulatum colonizes macrophages, which usually destroy invading microbes. Despite exposure to anti-microbial effectors in the host cell, H. capsulatum often persists in the host for many years after the acute infection resolves. We have used functional genomics to identify genes that are induced when H. capsulatum is exposed to reactive nitrogen intermediates, a common anti-microbial effector. One of these genes has homology to a nitric oxide reductase from a fungal pathogen of plants. We are using molecular genetic techniques to ascertain whether this gene allows H. capsulatum to survive exposure to toxic reactive nitrogen intermediates produced by host cells. We are studying the function of this gene to determine its role in disease and persistence in the host.

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