The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins ^1-4 . APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense ³ . We considered the possibility that intracellular members of the APOL1 family, against which extracellular trypanosomes could not have evolved resistance, could kill pathogenic T. brucei subspecies. Here we show that recombinant APOL3 (rAPOL3) kills all African trypanosomes, including T.b. rhodesiense, T.b. gambiense and the animal pathogens Trypanosoma evansi, Trypanosoma congolense and Trypanosoma vivax. However, rAPOL3 did not kill more distant trypanosomes such as Trypanosoma theileri or Trypanosoma cruzi. This trypanolytic potential was partially shared by rAPOL1 from Papio papio (rPpAPOL1). The differential killing ability of rAPOL3 and rAPOL1 was associated with a distinct dependence on acidic pH for activity. Due both to its instability and toxicity when injected into mice, rAPOL3 cannot be used for the treatment of infection, but an experimental rPpAPOL1 mutant inspired by APOL3 exhibited enhanced trypanolytic activity in vitro and the ability to completely inhibit T.b. gambiense infection in mice. We conclude that pH dependence influences the trypanolytic potential of rAPOLs.

中文翻译：

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具有低 pH 依赖性的 APOL 可以杀死所有非洲锥虫。

灵长类动物特异性血清蛋白载脂蛋白 L1 (APOL1) 是细胞死亡促进蛋白^1-4家族中唯一分泌的成员。APOL1 可杀死血液寄生虫布氏锥虫，但不能杀死人类昏睡病剂 Tb rhodesiense 和 Tb gambiense ³. 我们考虑了 APOL1 家族的细胞内成员（细胞外锥虫无法进化出抗性）可以杀死致病性布氏锥虫亚种的可能性。在这里，我们显示重组 APOL3 (rAPOL3) 杀死所有非洲锥虫，包括 Tb rhodesiense、Tb gambiense 和动物病原体伊氏锥虫、刚果锥虫和间日锥虫。然而，rAPOL3 并没有杀死更远的锥虫，例如泰勒锥虫或克氏锥虫。来自 Papio papio (rPpAPOL1) 的 rAPOL1 部分共享了这种锥虫分解潜力。rAPOL3 和rAPOL1 的不同杀伤能力与活性对酸性pH 的明显依赖性有关。由于其在注射到小鼠体内时的不稳定性和毒性，rAPOL3 不能用于治疗感染，但受 APOL3 启发的实验性 rPpAPOL1 突变体在体外表现出增强的锥虫分解活性和完全抑制小鼠冈比亚结核杆菌感染的能力。我们得出结论，pH 依赖性影响 rAPOL 的锥虫分解潜力。