Discussion

Humans are protected against infection from most African trypanosomes by lipoprotein complexes present in serum that contain the trypanolytic pore-forming protein, apolipoprotein L1 (APOL1). Two trypanosomes, Trypanosoma brucei rhodesiense and T.b. gambiense have evolved separate mechanisms that allow them to resist lysis by APOL1 and cause human African trypanosomiasis. Here we demonstrate the lytic ability of serum from a species of West African baboon, Papio papio, which is able to kill all sub-species of T. brucei including T. b. gambiense, the most common agent of human African trypanosomiasis. We show that this in vitro lytic ability is the result of a novel variant of APOL1, which is able to counteract the human serum resistance mechanisms of both T. b. rhodesiense and T. b. gambiense. The identification of a variant of APOL1 that can kill all T. brucei sub-species could form the basis of universal APOL1-based therapeutic strategies, effective against all pathogenic African trypanosomes.