Gonzalez Luis Miguel, Revuelta Belen, Gil Aitor, Terrón María C, Sachse Martin Christoph, Sotillo Javier, Luque Daniel, Rahman S M Raihan, Bastos Reginaldo G, Suarez Carlos Esteban, Montero Estrella
Parasitology Reference and Research Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Electron Microscopy Unit. Scientific and Technical Central Units, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
PLoS Negl Trop Dis. 2025 Aug 13;19(8):e0013401. doi: 10.1371/journal.pntd.0013401. eCollection 2025 Aug.
Babesia divergens is a blood-borne parasite that invades, replicates within and destroys red blood cells (RBCs) during its asexual life cycle, causing babesiosis in humans and cattle. This study focuses on BdP50, a putative B. divergens glycosylphosphatidylinositol-anchored protein involved in the parasite life cycle. BdP50 is found on the surface of B. divergens invasive parasites (merozoites) as well as on extracellular vesicles (Bd-derived EVs). These EVs are secreted by parasites cultured in fresh human RBCs and, in addition to BdP50, are enriched in human and parasite proteins, including proteins related to the parasite invasion process. BdP50 binds to RBCs and could mediate interactions of free merozoites and Bd-derived EVs with the host cell. Anti-BdP50 antibodies support this by blocking the BdP50 protein and inhibiting up to 88% of merozoite entry into naïve RBCs. This reinforces the role of BdP50 in parasite-host cell interactions and invasion. However, the inhibitory effect of BdP50 antibodies begins to gradually decrease slightly several hours after invasion, leading to a progressive increase in B. divergens infected RBCs over time. Consistent with these findings, our in vitro de novo infection assays showed that Bd-derived EVs, in addition to promoting parasite propagation, display proteins such as BdP50 that mimic the merozoite surface to likely attenuate the blocking effect of antibodies, thereby ensuring the parasite survival during subsequent rounds of invasion and growth. Given the role of BdP50 and Bd-derived EVs in the B. divergens life cycle, this study could have future implications for developing new approaches to interfere with parasite invasion proteins and Bd-derived EVs functions.
分歧巴贝斯虫是一种血源性病原体，在其无性生命周期中侵入红细胞（RBC）、在其中复制并破坏红细胞，从而在人和牛身上引发巴贝斯虫病。本研究聚焦于BdP50，这是一种推测参与分歧巴贝斯虫生命周期的糖基磷脂酰肌醇锚定蛋白。BdP50存在于分歧巴贝斯虫侵入性寄生虫（裂殖子）表面以及细胞外囊泡（Bd衍生的EVs）上。这些EVs由在新鲜人红细胞中培养的寄生虫分泌，除了BdP50外，还富含人和寄生虫蛋白，包括与寄生虫侵入过程相关的蛋白。BdP50与红细胞结合，并可介导游离裂殖子和Bd衍生的EVs与宿主细胞的相互作用。抗BdP50抗体通过阻断BdP50蛋白并抑制高达88%的裂殖子进入未感染的红细胞来支持这一点。这强化了BdP50在寄生虫-宿主细胞相互作用和侵入中的作用。然而，BdP50抗体的抑制作用在侵入后数小时开始逐渐略有下降，导致分歧巴贝斯虫感染的红细胞随时间逐渐增加。与这些发现一致，我们的体外从头感染试验表明，Bd衍生的EVs除了促进寄生虫繁殖外，还展示出诸如BdP50之类的蛋白，这些蛋白模仿裂殖子表面，可能会减弱抗体的阻断作用，从而确保寄生虫在随后的侵入和生长轮次中的存活。鉴于BdP50和Bd衍生的EVs在分歧巴贝斯虫生命周期中的作用，本研究可能对开发干扰寄生虫侵入蛋白和Bd衍生的EVs功能的新方法具有未来意义。
