The TgsGP Gene Is Essential for Resistance to Human Serum in Trypanosoma brucei gambiense

PLoS Pathogens

Rudo Kieft¹  Eric DeJesus¹  Stephen Hajduk¹  Pieter C. Steketee²  Anneli Cooper²  Paul Capewell²  Nicola Veitch²  Caroline Clucas²  Annette MacLeod²  William Weir² 

[1] Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, United States of America;Wellcome Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

关键词: Trypanosoma;    Trypanosoma brucei gambiense;    Cloning;    Trypanosoma brucei;    Reverse transcriptase-polymerase chain reaction;    Kinetoplasts;    Parasitic diseases;    Polymerase chain reaction;   

DOI  :  10.1371/journal.ppat.1003686

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY