The GPI biosynthetic pathway as a therapeutic target for African sleeping sickness

African sleeping sickness is a debilitating and often fatal disease caused by tsetse fly transmitted African trypanosomes. These extracellular protozo an parasites survive in the human bloodstream by virtue of a dense cell sur face coat made of variant surface glycoprotein. The parasites have a repert oire of several hundred immunologically distinct variant surface glycoprote ins and they evade the host immune response by antigenic variation. All var iant surface glycoproteins are anchored to the plasma membrane via glycosyl phosphatidylinositol membrane anchors and compounds that inhibit the assemb ly or transfer of these anchors could have trypanocidal potential. This art icle compares glycosylphosphatidylinositol biosynthesis in African trypanos omes and mammalian cells and identifies several steps that could be targets for the development of parasite-specific therapeutic agents. (C) 1999 Else vier Science B.V. All rights reserved.