抗疟药物通常只对部分种类的疟原虫有效,这是疟疾防治一直以来的难题。英国研究人员日前在破解这一难题方面取得进展,他们发现了一种对所有恶性疟原虫都有效的治疗途径。
英国桑格研究所等机构研究人员在《自然》杂志网站上报告说,他们发现疟原虫在人体血液中入侵红细胞的时候,红细胞上一种名为basigin的蛋白质和疟原虫表面一种名为PfRh5的蛋白质之间的联系是至关重要的,如果用药物阻碍它们之间建立联系,就可以防止疟原虫入侵红细胞,从而打断疟原虫传播疟疾的进程。
这一发现的重要意义在于,它对所有种类的恶性疟原虫都有效。据介绍,疟原虫非常“狡诈”,入侵红细胞的途径非常多样而富于变化,此前所发现的一些能防止疟原虫入侵红细胞的途径都只对部分疟原虫有效,而在本次研究中,研究人员测试了所有种类的恶性疟原虫,发现这个干预途径对它们都有效。
研究人员加文·赖特说,这相当于发现了疟原虫的“阿喀琉斯之踵”,完全改变了科研人员对疟原虫入侵进程的看法。研究人员认为可以在此基础上开发出更加有效的疟疾防治手段。(生物谷 Bioon.com)
doi:10.1038/nature10606
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Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum
Cécile Crosnier, Leyla Y. Bustamante, S. Josefin Bartholdson, Amy K. Bei, Michel Theron, Makoto Uchikawa, Souleymane Mboup, Omar Ndir, Dominic P. Kwiatkowski, Manoj T. Duraisingh, Julian C. Rayner & Gavin J. Wright
Erythrocyte invasion by Plasmodium falciparum is central to the pathogenesis of malaria. Invasion requires a series of extracellular recognition events between erythrocyte receptors and ligands on the merozoite, the invasive form of the parasite. None of the few known receptor–ligand interactions involved1, 2, 3, 4 are required in all parasite strains, indicating that the parasite is able to access multiple redundant invasion pathways5. Here, we show that we have identified a receptor–ligand pair that is essential for erythrocyte invasion in all tested P. falciparum strains. By systematically screening a library of erythrocyte proteins, we have found that the Ok blood group antigen, basigin, is a receptor for PfRh5, a parasite ligand that is essential for blood stage growth6. Erythrocyte invasion was potently inhibited by soluble basigin or by basigin knockdown, and invasion could be completely blocked using low concentrations of anti-basigin antibodies; importantly, these effects were observed across all laboratory-adapted and field strains tested. Furthermore, Oka− erythrocytes, which express a basigin variant that has a weaker binding affinity for PfRh5, had reduced invasion efficiencies. Our discovery of a cross-strain dependency on a single extracellular receptor–ligand pair for erythrocyte invasion by P. falciparum provides a focus for new anti-malarial therapies