Structure and function of trans-sialidase family ; its relation to the parasite lifecycle

转唾液酸酶家族的结构和功能；

• 批准号: 13670250
• 负责人: UEMURA Haruji
• 金额: $ 1.98万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670250/
• 关键词: Trans-sialidase; Trypanosoma; Chagas disease; African sleeping sickness; Cell invasion; GPI-anchor; Escape; シャガス病; シアル酸; 遺伝子ファミリー; シャガ病

The parasitic Trypanosomes can not synthesize sialic acid but express a unique enzyme, trans-sialidase (TS) in order to incorporate sialic acids on their surface. This enzyme has been shown to be important for parasite to survive in host defense environment and to invade to host cells. The TS are encoded by several gene families and its expression is strongly controlled by stage specific manor.We have presented that TS and parasite surface sialic acids are essential for the African trypanosome Trypanosoma brucei, to protect the parasite from the digestive condition in the mud-gut of Tsetse flies. T.brucei expresses TS at the insect stage. The parasite lacking sialic acids due to a defective generation of GPI-anchored trans-sialidase could not survive in the intestine, but regained the ability to survive when sialylated by means of soluble trans-sialidase.We also have shown that TS in T. cruzi is important for parasite escape from the paraitophorous vacuole (PV). T.cruzi trypomastigotes (TCT) and metacyclic trypomastigotes (MT) attached to and invaded mammalian host cells HeLa or CHO cells equally, but the former TCT escaped from the vacuole earlier than MT. The trypomastigote TS was expressed on the surface of metacyclic formed and used for cell invasion experiments. The transfected parasites could efficiently escaped from the PV and this result indicate that increased TS enzyme activity in TCT is important for efficient earlier exit from the PV to cytoplasm and subsequent differentiation into amastigotes.

寄生锥虫不能合成唾液酸，但表达一种独特的酶，转唾液酸酶（TS），以将唾液酸结合在其表面上。该酶对寄生虫在宿主防御环境中的生存和入侵宿主细胞具有重要作用。TS由几个基因家族编码，其表达受阶段特异性Manor的强烈控制，我们已经提出TS和寄生虫表面唾液酸对于非洲锥虫布氏锥虫是必需的，以保护寄生虫免受采采蝇泥肠中消化条件的影响。布氏锥虫在昆虫阶段表达TS。由于GPI锚定的转唾液酸酶产生缺陷而缺乏唾液酸的寄生虫不能在肠道中存活，但当通过可溶性转唾液酸酶进行唾液酸化时，寄生虫恢复了存活的能力。cruzi对于寄生虫逃离寄生泡（PV）是重要的。克氏锥虫锥鞭毛体（TCT）和亚循环锥鞭毛体（MT）均能附着并侵入宿主细胞HeLa和CHO，但前者比MT先从空泡中逃逸。将锥鞭毛体TS表达在所形成的后环的表面上，并用于细胞侵袭实验。转染的寄生虫可以有效地逃离PV，这一结果表明TCT中TS酶活性的增加对于有效地早期离开PV到细胞质和随后分化为无鞭毛体是重要的。

项目成果

Parasite-derived trans-sialidase binds to heart tissue in Trypanosoma cruzi-infected animals.

寄生虫衍生的反式唾液酸酶与克氏锥虫感染动物的心脏组织结合。

• 发表时间: 2004
• 期刊: Microb Pathog. 37
• 作者: Alcantara-Neves;M.M. et al.
• 通讯作者: M.M. et al.

African trypanosomes coat sialic acid taken from the host to survive in tsetse fly vectors.

非洲锥虫包裹着取自宿主的唾液酸，以便在采采蝇媒介中生存。

• 发表时间: 2004
• 期刊: J. Exp. Med. 199
• 作者: Nagamune;K.;Acosta-Serrano;A.;Uemura;H.;Brun;R.;Kunz-Renggli;C.;Maeda;Y.;Ferguson;M.A.J.;Kinoshita;T.
• 通讯作者: T.