Abstract
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). The human-infective trypanosomes, Trypanosoma brucei rhodesiense in East Africa and T. b. gambiense in West Africa have separately evolved mechanisms that allow them to resist APOL1-mediated lysis and cause human African trypanosomiasis, or sleeping sickness, in man. Recently, APOL1 variants were identified from a subset of Old World monkeys, that are able to lyse East African T. b. rhodesiense, by virtue of C-terminal polymorphisms in the APOL1 protein that hinder that parasite’s resistance mechanism. Such variants have been proposed as candidates for developing therapeutic alternatives to the unsatisfactory anti-trypanosomal drugs currently in use. Here we demonstrate the in vitro lytic ability of serum and purified recombinant protein of an APOL1 ortholog from the West African Guinea baboon (Papio papio), which is able to lyse examples of all sub-species of T. brucei including T. b. gambiense group 1 parasites, the most common agent of human African trypanosomiasis. The identification of a variant of APOL1 with trypanolytic ability for both human-infective T. brucei sub-species could be a candidate for universal APOL1-based therapeutic strategies, targeted against all pathogenic African trypanosomes.
Highlights
African trypanosomes continue to exert a significant barrier to agricultural production and rural development across sub-Saharan Africa [1]
Humans are naturally resistant to infection by most African trypanosomes species because of a lytic protein component in their blood, called Apolipoprotein L1 (APOL1)
APOL1 Variant That Kills T. b. gambiense that are able to kill the East African human disease-causing sub-species. These APOL1 variants form the basis of current attempts to create novel therapeutic interventions that can kill both animal and human-infective trypanosomes. We show that another variant of the same protein from a West African baboon species is able to kill, East African human-infective trypanosomes, and the West African parasites, which causes the majority of human African trypanosomiasis cases
Summary
African trypanosomes continue to exert a significant barrier to agricultural production and rural development across sub-Saharan Africa [1]. Gambiense, have evolved distinct processes to resist this lysis and cause the debilitating and often fatal human form of African trypanosomiasis, known as sleeping sickness. Rhodesiense sub-species, located in Eastern and Southern Africa, results in a more rapidly progressing, acute infection [2,3]. Decades of drug development for African trypanosomiasis has produced safer refinements of existing therapies [7,8] and a number of promising novel drug candidates [9,10,11], but as yet no new anti-trypanosomal therapy has successfully passed phase III clinical trials. The recent discovery of primate serum proteins that are able to kill both animal and human-infective trypanosomes is offering opportunities for novel therapeutic approaches [14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
