1] Institut Pasteur, Malaria Biology and Genetics Unit, Department of Parasitology and Mycology, 28 Rue du Dr Roux, Paris, France [2].
Nat Commun. 2013;4:2552. doi: 10.1038/ncomms3552.
Apicomplexan parasites invade host cells by forming a ring-like junction with the cell surface and actively sliding through the junction inside an intracellular vacuole. Apical membrane antigen 1 is conserved in apicomplexans and a long-standing malaria vaccine candidate. It is considered to have multiple important roles during host cell penetration, primarily in structuring the junction by interacting with the rhoptry neck 2 protein and transducing the force generated by the parasite motor during internalization. Here, we generate Plasmodium sporozoites and merozoites and Toxoplasma tachyzoites lacking apical membrane antigen 1, and find that the latter two are impaired in host cell attachment but the three display normal host cell penetration through the junction. Therefore, apical membrane antigen 1, rather than an essential invasin, is a dispensable adhesin of apicomplexan zoites. These genetic data have implications on the use of apical membrane antigen 1 or the apical membrane antigen 1-rhoptry neck 2 interaction as targets of intervention strategies against malaria or other diseases caused by apicomplexans.
顶复门寄生虫通过与细胞膜形成环状连接,并在细胞内空泡中主动滑过连接点,从而入侵宿主细胞。顶膜抗原 1 在顶复门寄生虫中保守存在,是一种长期以来的疟疾候选疫苗。它被认为在宿主细胞穿透过程中具有多种重要作用,主要是通过与棒状体颈 2 蛋白相互作用来构建连接点,并传递寄生虫马达在内化过程中产生的力。在这里,我们生成了缺乏顶膜抗原 1 的疟原虫孢子和裂殖子以及刚地弓形虫速殖子,发现后两者在宿主细胞附着方面受损,但这三种寄生虫都能通过连接点正常穿透宿主细胞。因此,顶膜抗原 1 不是顶复门动合子的必需入侵素,而是一种可有可无的黏附素。这些遗传数据表明,顶膜抗原 1 或顶膜抗原 1-棒状体颈 2 相互作用可作为针对疟疾或其他由顶复门寄生虫引起的疾病的干预策略的靶点。