Molecular one-upmanship

Abstract

Pathogens and their hosts engage in perpetual molecular arms races. In one such evolutionary stand-off, the protagonists are trypanosome parasites and a human immune complex based on a high-density lipoprotein. See Letter p.430 Humans are normally protected against trypanosomal pathogens by the serum antiparasitic molecule apolipoprotein LI (APOL1). But two Trypanosoma brucei subspecies — rhodesiense and gambiense — can resist APOL1 and it is these that cause almost all human sleeping sickness cases. This paper describes the mechanism by which T. b. gambiense resists APOL1. Three complementary processes are involved: reduced APOL1 uptake, increased APOL1 degradation and APOL1 target membrane modification by a specific resistance factor. This resistance can be bypassed under some conditions, opening up new possibilities for intervention against the parasite.