The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense

Capewell, P., Clucas, C., DeJesus, E., Kieft, R., Hajduk, S., Veitch, N., Steketee, P.C., Cooper, A., Weir, W. and MacLeod, A. (2013) The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. PLoS Pathogens, 9(10), e1003686. (doi:10.1371/journal.ppat.1003686) (PMID:24098129) (PMCID:PMC3789759)

Capewell, P., Clucas, C., DeJesus, E., Kieft, R., Hajduk, S., Veitch, N., Steketee, P.C., Cooper, A., Weir, W. and MacLeod, A. (2013) The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. PLoS Pathogens, 9(10), e1003686. (doi:10.1371/journal.ppat.1003686) (PMID:24098129) (PMCID:PMC3789759)

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Abstract

Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as T. b. brucei, are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors (TLF-1 and TLF-2). Understanding how T. b. gambiense overcomes these factors and infects humans is of major importance in the fight against this disease. Previous work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a T. b. gambiense specific gene, TgsGP, which had previously been suggested, but not shown, to be involved in serum resistance. We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to human serum and recombinant APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in T. b. gambiense.

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: Capewell, P., Clucas, C., DeJesus, E., Kieft, R., Hajduk, S., Veitch, N., Steketee, P.C., Cooper, A., Weir, W., and MacLeod, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:PLoS Pathogens
Publisher:Public Library of Science
ISSN:1553-7366
ISSN (Online):1553-7366
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS Pathogens 9(10):e1003686
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
371796The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOME)085349/Z/08/ZIII - PARASITOLOGY
371798The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOME)085349/B/08/ZIII - PARASITOLOGY