Trypanosoma brucei brucei, unlike the human pathogens Tau beta rhodesiense and Tau gambiense, is lysed by human serum. Sensitivity to human serum is the only method which allows distinction between the cattle and human African trypanosomes. We have identified two distinct trypanolytic fractions in normal human serum (NHS) which differ physically, biochemically and with regard to their inhibition by serum factors. Significantly, an HDL-like trypanolytic factor (TLF1) described by others is not active in NHS, and only becomes lytic upon inhibitor removal during isolation procedures. It is proposed to characterize the more physiologically relevant lytic factor in human serum, and to determine the mechanism(s) by which parasites are killed by both factors. Data indicates that a mechanism of lysis may involve oxidative stress and subsequent programmed cell death, and these possibilities will be tested directly. This work may open new perspectives for the chemotherapy of trypanosomiasis. Understanding of the mechanisms of cytotoxicity and the affected metabolic pathways may provide new approaches for development of specific drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI040206-02
Application #
2887270
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Fairfield, Alexandra
Project Start
1998-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
New York University
Department
Pathology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10016