Human sleeping sickness — African trypanosomiasis — is caused by the protozoan parasite Trypanosoma bruceirhodesiense and is transmitted to humans through the bite of infected tsetse flies. Human serum contains a trypanosome lytic factor that can prevent infection by susceptible trypanosomes. Some T. b. rhodesiense strains exhibit resistance to this factor mediated by a gene encoding a truncated form of the variant surface glycoprotein serum resistance associated protein (SRA), but the exact molecular mechanisms behind this resistance have been unclear. In the March 6 Nature, Luc Vanhamme and colleagues at the University of Brussels, Belgium, reveal how the parasite overcomes natural human defenses (Nature, 422:83-87, March 6, 2003).
Vanhamme et al. localized SRA to the lysosome and identified the human-specific serum protein apoL-I — an apolipoprotein associated with high density lipoprotein — as the human trypanolytic factor. The amino-terminal α-helix of SRA bound to a carboxy-terminal α-helix of apoL-I, and ...