Mycobacterium tuberculosis, the primary etiologic agent of tuberculosis, causes one of the most important diseases in the world from the standpoint of human morbidity and mortality. In the past decade, it has emerged as a major opportunistic infection in patients with AIDS. Multidrug-resistant M. tuberculosis poses a major threat to the public health. The development of new preventative or therapeutic strategies to combat this pathogen requires more knowledge about M. tuberculosis molecules that play a key role in bacterial physiology and pathogenesis. Such molecules include exochelins, low molecular weight iron-binding peptides of M. tuberculosis, about which little is known. In preliminary investigations, we have succeeded in purifying the major exochelins of M. tuberculosis so as to allow their structural, biological, and immunological characterization. This proposal seeks to enhance our understanding of the composition and structure of exochelins, their role in extracellular growth and in intracellular growth in macrophages, and the immune response to them. Hopefully, such studies will lead to new approaches to preventing and treating tuberculosis.
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