A primate APOL1 variant that kills Trypanosoma brucei gambiense

Cooper, A., Capewell, P., Clucas, C., Veitch, N., Weir, W. , Thomson, R., Raper, J. and MacLeod, A. (2016) A primate APOL1 variant that kills Trypanosoma brucei gambiense. PLoS Neglected Tropical Diseases, 10(8), e0004903. (doi:10.1371/journal.pntd.0004903) (PMID:27494254) (PMCID:PMC4975595)

Cooper, A., Capewell, P., Clucas, C., Veitch, N., Weir, W. , Thomson, R., Raper, J. and MacLeod, A. (2016) A primate APOL1 variant that kills Trypanosoma brucei gambiense. PLoS Neglected Tropical Diseases, 10(8), e0004903. (doi:10.1371/journal.pntd.0004903) (PMID:27494254) (PMCID:PMC4975595)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLeod, Professor Annette and Weir, Dr William and Capewell, Dr Paul and Cooper, Dr Anneli and Veitch, Dr Nicola and Clucas, Dr Caroline
Authors: Cooper, A., Capewell, P., Clucas, C., Veitch, N., Weir, W., Thomson, R., Raper, J., and MacLeod, A.
Subjects:?? Research Article ??
?? Biology and life sciences ??
?? Medicine and health sciences ??
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2016 Cooper et al.
First Published:First published in PLoS Neglected Tropical Diseases 10(8):e0004903
Publisher Policy:Reproduced under a creative commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
558211The origins and mechanisms of human infectivity in African trypanosomes.Annette MacLeodWellcome Trust (WELLCOME)095201/Z/10/ZRI BIODIVERSITY ANIMAL HEALTH & COMPMED
371796The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOME)085349/Z/08/ZIII - PARASITOLOGY