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

Paul Capewell, Caroline Clucas, Eric DeJesus, Rudo Kieft, Stephen Hajduk, Nicola Veitch, Pieter C Steketee, Anneli Cooper, William Weir, Annette MacLeod

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)e1003686
JournalPLoS Pathogens
Volume9
Issue number10
DOIs
Publication statusPublished - 3 Oct 2013

Keywords

  • Apolipoprotein L1
  • Apolipoproteins/genetics
  • Humans
  • Lipoproteins, HDL/genetics
  • Protozoan Proteins/genetics
  • Trypanosoma brucei gambiense/genetics
  • Trypanosomiasis, African/genetics

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