Wellcome Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
PLoS Pathog. 2013;9(10):e1003686. doi: 10.1371/journal.ppat.1003686. Epub 2013 Oct 3.
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.
布氏冈比亚锥虫引起了 97%的非洲昏睡病病例，这是撒哈拉以南非洲的一种致命疾病。大多数锥虫物种，如 T. b. brucei，由于通过两种锥虫溶素因子（TLF-1 和 TLF-2）传递的血清蛋白载脂蛋白-L1（APOL1）而无法感染人类。了解 T. b. 冈比亚锥虫如何克服这些因素并感染人类，对于对抗这种疾病至关重要。以前的工作表明，T. b. 冈比亚锥虫未能摄取 TLF-1 有助于抵抗 TLF-1，尽管还需要另一种机制来克服 TLF-2。在这里，我们研究了一种 T. b. 冈比亚锥虫特异性基因 TgsGP，该基因先前被认为但未被证明与血清抗性有关。我们表明，TgsGP 对于抵抗裂解是必不可少的，因为在 T. b. 冈比亚锥虫中缺失 TgsGP 会使寄生虫对人血清和重组 APOL1 敏感。在摄取 TLF-1 进行修饰的 T. b. 冈比亚锥虫中缺失 TgsGP 显示对 TLF-1、APOL1 和人血清敏感。将 TgsGP 重新引入敲除寄生虫系中恢复了抗性。我们得出结论，TgsGP 是 T. b. 冈比亚锥虫对人血清抗性所必需的。
