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, Professor Willie and Capewell, Dr Paul and Cooper, Dr Anneli and Veitch, Dr Nicola and O'Connell, 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | PLoS Pathogens |
| Publisher: | Public Library of Science |
| ISSN: | 1553-7366 |
| ISSN (Online): | 1553-7374 |
| 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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