Ng Yee Ling, Lee Wenn-Chyau, Lau Yee-Ling, Fong Mun Yik
Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia.
A*STAR Infectious Diseases Labs, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.
Trop Med Infect Dis. 2023 Jan 10;8(1):56. doi: 10.3390/tropicalmed8010056.
has emerged as an important zoonotic parasite that causes persistent symptomatic malaria in humans. The signs and symptoms of malaria are attributed to the blood stages of the parasites, which start from the invasion of erythrocytes by the blood stage merozoites. The apical membrane protein 1 (AMA-1) plays an important role in the invasion. In this study, we constructed and expressed recombinant PkAMA-1 domain II (PkAMA-1-DII) representing the predominant haplotypes from Peninsular Malaysia and Malaysian Borneo and raised specific antibodies against the recombinant proteins in rabbits. Despite the minor amino acid sequence variation, antibodies raised against haplotypes from Peninsular Malaysia and Malaysian Borneo demonstrated different invasion inhibition (46.81% and 39.45%, respectively) to A1-H.1, a reference strain derived from Peninsular Malaysia. Here, we demonstrated how a minor variation in a conserved parasite protein could cast a significant impact on parasite invasion biology, suggesting a complex host-switching of from different locations. This may challenge the implementation of a standardized One Health approach against the transmission of knowlesi malaria.
已成为一种重要的人畜共患寄生虫，可导致人类持续性症状性疟疾。疟疾的体征和症状归因于寄生虫的血液阶段，这始于血液阶段裂殖子侵入红细胞。顶膜蛋白1（AMA-1）在入侵过程中起重要作用。在本研究中，我们构建并表达了代表马来西亚半岛和马来西亚婆罗洲主要单倍型的重组PkAMA-1结构域II（PkAMA-1-DII），并在兔体内产生了针对重组蛋白的特异性抗体。尽管氨基酸序列存在微小差异，但针对马来西亚半岛和马来西亚婆罗洲单倍型产生的抗体对源自马来西亚半岛的参考菌株A1-H.1表现出不同的入侵抑制作用（分别为46.81%和39.45%）。在此，我们证明了保守寄生虫蛋白中的微小变异如何对寄生虫入侵生物学产生重大影响，表明来自不同地点的寄生虫存在复杂的宿主转换。这可能会对实施针对诺氏疟原虫传播的标准化“同一健康”方法构成挑战。
