A novel Plasmodium falciparum rhoptry associated adhesin mediates erythrocyte invasion through the sialic-acid dependent pathway.
A novel Plasmodium falciparum rhoptry associated adhesin mediates erythrocyte invasion through the sialic-acid dependent pathway.
复制标题
一种新型的恶性疟原虫相关的粘附素通过唾液酸依赖性途径介导红细胞侵袭。
DOI：
10.1038/srep29185
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发表时间：
2016-07-07
影响因子：
4.6
通讯作者：
Gaur D
中科院分区：
文献类型：
--
作者：
Anand G;Reddy KS;Pandey AK;Mian SY;Singh H;Mittal SA;Amlabu E;Bassat Q;Mayor A;Chauhan VS;Gaur D
恶性疟原虫裂殖子侵袭红细胞是血液期感染和疟疾发病的中心环节。这一复杂的过程由多种寄生虫粘附素协调，这些粘附素与红细胞受体结合，并通过几种不同的途径介导入侵。恶性疟原虫在血液期表达2700个基因，其中许多基因的身份和功能尚不清楚。在这里，我们已经鉴定并鉴定了一种新的恶性疟原虫棒状杆菌相关粘附素(PFRA)，它通过唾液酸依赖的途径介导红细胞侵袭。PFRA似乎扮演着重要的功能角色，因为它在不同的疟原虫物种中是保守的。它定位于裂殖子，并进一步转移到裂殖子表面。天然的和重组的PFRA都以唾液酸依赖、胰凝乳酶和胰蛋白酶抵抗的方式与红细胞特异性结合，这种结合被证实在红细胞侵袭中起作用的PFRA抗体所阻断。PFRA抗体可抑制红细胞的侵袭，与其他寄生虫配体的抗体联合可产生相加的抑制作用，从而证实其在红细胞侵袭中的重要作用。因此，我们鉴定了一种新的恶性疟原虫粘附素，它能与含有红细胞受体的唾液酸结合。我们的观察证实了通过同时靶向参与交替入侵途径的多个保守的裂殖子抗原来阻止恶性疟原虫红细胞入侵的策略。
Erythrocyte invasion by Plasmodium falciparum merozoites is central to blood-stage infection and malaria pathogenesis. This intricate process is coordinated by multiple parasite adhesins that bind erythrocyte receptors and mediate invasion through several alternate pathways. P. falciparum expresses 2700 genes during the blood-stages, of which the identity and function of many remains unknown. Here, we have identified and characterized a novel P. falciparum rhoptry associated adhesin (PfRA) that mediates erythrocyte invasion through the sialic-acid dependent pathway. PfRA appears to play a significant functional role as it is conserved across different Plasmodium species. It is localized in the rhoptries and further translocated to the merozoite surface. Both native and recombinant PfRA specifically bound erythrocytes in a sialic-acid dependent, chymotrypsin and trypsin resistant manner, which was abrogated by PfRA antibodies confirming a role in erythrocyte invasion. PfRA antibodies inhibited erythrocyte invasion and in combination with antibodies against other parasite ligands produced an additive inhibitory effect, thus validating its important role in erythrocyte invasion. We have thus identified a novel P. falciparum adhesin that binds with a sialic acid containing erythrocyte receptor. Our observations substantiate the strategy to block P. falciparum erythrocyte invasion by simultaneously targeting multiple conserved merozoite antigens involved in alternate invasion pathways.