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Plasmodium falciparum Field Isolates Commonly Use Erythrocyte Invasion Pathways That Are Independent of Sialic Acid Residues of Glycophorin A

机译:恶性疟原虫野外分离株通常使用独立于糖蛋白A的唾液酸残基的红细胞侵入途径

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Erythrocyte invasion by malaria parasites is mediated by specific molecular interactions. Sialic acid residues of glycophorin A are used as invasion receptors by Plasmodium falciparum. In vitro invasion studies have demonstrated that some cloned P. falciparum lines can use alternate receptors independent of sialic acid residues of glycophorin A. It is not known if invasion by alternate pathways occurs commonly in the field. In this study, we used in vitro growth assays and erythrocyte invasion assays to determine the invasion phenotypes of 15 P. falciparum field isolates. Of the 15 field isolates tested, 5 multiply in both neuraminidase and trypsin-treated erythrocytes, 3 multiply in neuraminidase-treated but not trypsin-treated erythrocytes, and 4 multiply in trypsin-treated but not neuraminidase-treated erythrocytes; 12 of the 15 field isolates tested use alternate invasion pathways that are not dependent on sialic acid residues of glycophorin A. Alternate invasion pathways are thus commonly used by P. falciparum field isolates. Typing based on two polymorphic markers, MSP-1 and MSP-2, and two microsatellite markers suggests that only 1 of the 15 field isolates tested contains multiple parasite genotypes. Individual P. falciparum lines can thus use multiple invasion pathways in the field. These observations have important implications for malaria vaccine development efforts based on EBA-175, the P. falciparumprotein that binds sialic acid residues of glycophorin A during invasion. It may be necessary to target parasite ligands responsible for the alternate invasion pathways in addition to EBA-175 to effectively block erythrocyte invasion by P. falciparum.
机译:疟原虫入侵红细胞是由特定的分子相互作用介导的。糖原A的唾液酸残基被恶性疟原虫用作入侵受体。体外入侵研究表明,某些克隆的 P。恶性疟原虫系可以使用独立于糖蛋白A唾液酸残基的替代受体。目前尚不知道是否通过替代途径入侵该病。在这项研究中,我们使用了体外生长测定和红细胞侵袭测定来确定15 P的侵袭表型。恶性疟原虫。在测试的15个分离株中,神经氨酸酶和胰蛋白酶处理的红细胞中有5倍,神经氨酸酶处理但未经胰蛋白酶处理的红细胞中有3倍,而胰蛋白酶处理但未经神经氨酸酶处理的红细胞中有4倍。测试的15个田间分离株中有12个使用不依赖于糖蛋白A唾液酸残基的替代入侵途径。因此, P通常使用替代入侵途径。恶性疟原虫。基于两个多态性标记MSP-1和MSP-2以及两个微卫星标记的分型表明,所测试的15个田间分离株中只有1个含有多种寄生虫基因型。个人 P。因此,恶性疟原虫系可以在田间使用多种入侵途径。这些观察结果对基于EBA-175( P)的疟疾疫苗开发工作具有重要意义。在侵袭过程中结合糖蛋白A唾液酸残基的恶性蛋白质。除EBA-175外,可能有必要靶向负责替代入侵途径的寄生虫配体,以有效地阻止 P入侵红细胞。恶心

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