The <i>TgsGP</i> Gene Is Essential for Resistance to Human Serum in <i>Trypanosoma brucei gambiense</i>

<div><p><i>Trypanosoma brucei gambiense</i> causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as <i>T. b. brucei</i>, 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 <i>T. b. gambiense</i> 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 <i>T. b. gambiense</i> contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a <i>T. b. gambiense</i> specific gene, <i>TgsGP</i>, which had previously been suggested, but not shown, to be involved in serum resistance. We show that <i>TgsGP</i> is essential for resistance to lysis as deletion of <i>TgsGP</i> in <i>T. b. gambiense</i> renders the parasites sensitive to human serum and recombinant APOL1. Deletion of <i>TgsGP</i> in <i>T. b. gambiense</i> modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing <i>TgsGP</i> into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in <i>T. b. gambiense</i>.</p>