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.
Highlights
Throughout their evolution in sub-Saharan Africa, humans have been under assault by a range of different pathogens
Previous work indicated that a failure to take up some trypanolytic factors by T. b. gambiense contributes to resistance, other mechanisms are involved
We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to most trypanolytic factors
Summary
Throughout their evolution in sub-Saharan Africa, humans have been under assault by a range of different pathogens. The principle pathogenic species in Africa are Trypanosoma brucei, T. congolense and T. vivax, only Trypanosoma brucei sub-species are able to infect humans. Components of the innate immune system contribute significantly to defence against these organisms [3]. Critical to these defences is the serum protein apolipoprotein L1 (APOL1) found in some catarrhine primates, including humans [4,5]. The protein is able to kill the majority of trypanosome species in a dose-dependent manner [5]. APOL1 is delivered to parasites in two fractions of the high-density lipoprotein (HDL) component of serum, termed trypanolytic factor 1 and 2 (TLF-1 and TLF-2) [6]. A proportion of TLF-2 enters trypanosomes via HpHbR, an alternate route contributes to uptake [11]
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