title: Differences between Trypanosoma brucei gambiense groups 1 and 2 in their resistance to killing by trypanolytic factor 1.
abstract: BACKGROUND
  The three sub-species of Trypanosoma brucei are important pathogens of sub-Saharan Africa. T. b. brucei is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. T. b. rhodesiense and T. b. gambiense are able to resist lysis by TLF. There are two distinct sub-groups of T. b. gambiense that differ genetically and by human serum resistance phenotypes. Group 1 T. b. gambiense have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 T. b. gambiense are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (HpHbR)) gene. Here we investigate if this is also true in group 2 parasites.
  
  
  METHODS
  Isogenic resistant and sensitive group 2 T. b. gambiense were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the HpHbR gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to T. b. brucei. Both resistant and sensitive group 2, as well as group 1 T. b. gambiense, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.
  
  
  CONCLUSIONS
  Our data indicate that, despite group 1 T. b. gambiense avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 T. b. gambiense is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 T. b. gambiense variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of HpHbR. Thus there are differences in the mechanism of human serum resistance between T. b. gambiense groups 1 and 2.
authors: College of Medical, Veterinary and Biological Sciences, Wellcome Trust Centre for Molecular Parasitology, University of Glasgow, Glasgow, United Kingdom.
authors: Paul
authors: P
authors: Capewell
authors: Nicola J
authors: NJ
authors: Veitch
authors: C Michael R
authors: CM
authors: Turner
authors: Jayne
authors: J
authors: Raper
authors: Matthew
authors: M
authors: Berriman
authors: Stephen L
authors: SL
authors: Hajduk
authors: Annette
authors: A
authors: MacLeod
mesh_terms: D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000276:immunology / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D006801:Humans; D008075:Lipoproteins, HDL / Q000276:immunology / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D044967:Serum / Q000276:immunology / Q000469:parasitology; D014347:Trypanosoma brucei gambiense / Q000145:classification / Q000187:drug effects* / Q000276:immunology / Q000502:physiology
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D001688:Biological Products; D008075:Lipoproteins, HDL; C434063:TLF1 protein, human