CONTROL OF LEISHMANIA BY PROGRAMMED CELL DEATH (APOPTOSIS)

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The Leishmania parasite causes human disease with clinical symptoms ranging from-self healing cutaneous lesions to a fatal visceral infection. Additionally, in endemic areas, people infected with HIV are especially prone to Leishmania infection. The lack of understanding of cell biology and pathogenic mechanisms of this parasite makes the task of controlling this grave, worldwide health risk difficult. Closer to home it is particularly of concern to U.S. military personnel, their families and other travellers visiting or living in the endemic areas. To find novel methods for control of this pathogen,we have initiated study to understand the mechanism of programmed cell death (apoptosis) in Leishmania. We have demonstrated that Leishmania cell death induced by heat shock or treatment with one of the anti-leishmanial drugs,pentastam, bears some similarities to classical apoptosis seen in mammalian cells. We are seeking more definitive evidence of the existence of an apoptotic program in these parasites by cloning Leishmanial homolgues of known apototic genes conserved from nematodes to humans. Next,we plan to manipulate apoptotic genes in Leishmania so as to alter the cell death pathway in Leishmania parasite thus can be eliminated with ease by the currently availabe drugs and has less toxic side effects commonly asociated with these therapies.