Heparin interacts with elongation factor 1α of Cryptosporidium parvum and inhibits invasion.
Heparin interacts with elongation factor 1α of Cryptosporidium parvum and inhibits invasion.
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DOI：
10.1038/srep11599
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发表时间：
2015-07-01
影响因子：
4.6
通讯作者：
Kato K
中科院分区：
文献类型：
--
作者：
Inomata A;Murakoshi F;Ishiwa A;Takano R;Takemae H;Sugi T;Cagayat Recuenco F;Horimoto T;Kato K
微小隐孢子虫是一种顶端复合体寄生虫，可在人类和其他哺乳动物中引起严重的水样腹泻和隐孢子虫病。微小隐孢子虫侵袭胃肠道上皮细胞，胃肠道上皮细胞表面有丰富的糖胺聚糖。然而，对微小弧菌和糖胺多聚糖之间的相互作用知之甚少。在这项研究中，我们评估了硫酸多糖对微小弧菌侵袭宿主细胞的抑制作用，并鉴定了与硫酸多糖相互作用的寄生虫配体。在所测试的五种硫酸多糖中，肝素对寄生虫入侵的抑制作用最强，且呈剂量依赖关系。缺乏硫酸乙酰肝素的细胞对微小弧菌感染的敏感性较低。我们进一步鉴定了31种可能与肝素相互作用的寄生虫蛋白。其中，我们证实微小弧菌延长因子1α(CpEF1α)与肝素和Hct-8细胞表面结合，在微小弧菌侵袭过程中起作用。我们的结果进一步加深了我们对微小隐孢子虫感染的分子基础的理解，并将有助于抗隐孢子虫药物的开发。
Cryptosporidium parvum is an apicomplexan parasite that can cause serious watery diarrhea, cryptosporidiosis, in human and other mammals. C. parvum invades gastrointestinal epithelial cells, which have abundant glycosaminoglycans on their cell surface. However, little is known about the interaction between C. parvum and glycosaminoglycans. In this study, we assessed the inhibitory effect of sulfated polysaccharides on C. parvum invasion of host cells and identified the parasite ligands that interact with sulfated polysaccharides. Among five sulfated polysaccharides tested, heparin had the highest, dose-dependent inhibitory effect on parasite invasion. Heparan sulfate-deficient cells were less susceptible to C. parvum infection. We further identified 31 parasite proteins that potentially interact with heparin. Of these, we confirmed that C. parvum elongation factor 1α (CpEF1α), which plays a role in C. parvum invasion, binds to heparin and to the surface of HCT-8 cells. Our results further our understanding of the molecular basis of C. parvum infection and will facilitate the development of anti-cryptosporidial agents.
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DOI：
10.1083/jcb.123.3.759
发表时间：
1993-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Love DC;Esko JD;Mosser DM
通讯作者：
Mosser DM
影响因子：
15.9
作者：
Esko, JD;Lindahl, U
通讯作者：
Lindahl, U
影响因子：
2.9
作者：
Copeland, Ronald;Balasubramaniam, Arun;Liu, Jian
通讯作者：
Liu, Jian
影响因子：
3.9
作者：
CARVALHO, MDD;CARVALHO, JF;MERRICK, WC
通讯作者：
MERRICK, WC
影响因子：
4.8
作者：
Kobayashi, Kyousuke;Kato, Kentaro;Akashi, Hiroomi
通讯作者：
Akashi, Hiroomi