The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1003686 |
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| author | Paul Capewell Caroline Clucas Eric DeJesus Rudo Kieft Stephen Hajduk Nicola Veitch Pieter C Steketee Anneli Cooper William Weir Annette MacLeod |
| author_facet | Paul Capewell Caroline Clucas Eric DeJesus Rudo Kieft Stephen Hajduk Nicola Veitch Pieter C Steketee Anneli Cooper William Weir Annette MacLeod |
| author_sort | Paul Capewell |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ddf283bedbe2423f9c8f2ebbe2e5b9aa |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-ddf283bedbe2423f9c8f2ebbe2e5b9aa2025-08-20T02:34:09ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-01910e100368610.1371/journal.ppat.1003686The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense.Paul CapewellCaroline ClucasEric DeJesusRudo KieftStephen HajdukNicola VeitchPieter C SteketeeAnneli CooperWilliam WeirAnnette MacLeodTrypanosoma 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.https://doi.org/10.1371/journal.ppat.1003686 |
| spellingShingle | Paul Capewell Caroline Clucas Eric DeJesus Rudo Kieft Stephen Hajduk Nicola Veitch Pieter C Steketee Anneli Cooper William Weir Annette MacLeod The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. PLoS Pathogens |
| title | The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. |
| title_full | The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. |
| title_fullStr | The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. |
| title_full_unstemmed | The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. |
| title_short | The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense. |
| title_sort | tgsgp gene is essential for resistance to human serum in trypanosoma brucei gambiense |
| url | https://doi.org/10.1371/journal.ppat.1003686 |
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