美国斯坦福大学医学院和加利福尼亚大学旧金山分校科学家通过一种新奇的“驯化”技术，让疟原虫必须依赖一种外来化学物质的供给才能活命，造出了一种“驯化疟原虫”。这种驯化疟原虫毒性大大减弱，并可能激发人体免疫系统反应，从而为开发首个抗疟疾疫苗提供了依据。该研究发表在8月30日的《公共科学图书馆—生物学》上。
疟原虫是一种单细胞变形虫，能导致疟疾。它们在蚊子体内、人体肝脏和血液中表现为不同的外形，以躲过免疫系统攻击。它们在人体肝脏内不显出症状，进入红细胞后会大量繁殖，使红细胞破碎，造成了病人冷热交替的症状。
研究人员发现，疟原虫进入血细胞后，要想存活必须依赖一种基本物质异戊烯焦磷酸（IPP）。正常情况下，IPP由一种独特的细胞器apicoplast合成供给，而这种细胞器是疟原虫独有的。
他们给血液阶段的疟原虫饲喂了一种抗生素，这种抗生素能让疟原虫与apicoplast分离，使它们最终死亡，但只用这种抗生素疗效很慢。如果把抗生素和IPP共同加入培养基，疟原虫仍会大量繁殖。
“这表明在apicoplast合成的多种物质中，IPP是疟原虫在血液阶段唯一真正需要的。”斯坦福大学病理学系的艾伦·雅解释说，由于哺乳动物制造IPP的途径和疟原虫完全不同，所以能破坏疟原虫合成IPP功能的药物，并不会损害人类细胞合成IPP的能力，也能清除疟原虫。
疟原虫每年造成大约100万人死亡，世界上每年新发的疟疾病例超过2.5亿，目前尚无有效的疟疾疫苗。尽管青蒿素仍然有效，但据报道已发现了有抗药性的疟原虫。艾伦·雅说：“如果抗药性疟原虫流行开来，我们会陷入大麻烦，因为几乎所有的疗法都是基于青蒿素。而apicoplast是重要的药物靶点，瞄准其功能是开发抵抗疟疾疗法的新方向。”(生物谷 Bioon.com)
doi:10.1371/journal.pbio.1001138
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Chemical Rescue of Malaria Parasites Lacking an Apicoplast Defines Organelle Function in Blood-Stage Plasmodium falciparum
Ellen Yeh, Joseph L. DeRisi
Plasmodium spp parasites harbor an unusual plastid organelle called the apicoplast. Due to its prokaryotic origin and essential function, the apicoplast is a key target for development of new anti-malarials. Over 500 proteins are predicted to localize to this organelle and several prokaryotic biochemical pathways have been annotated, yet the essential role of the apicoplast during human infection remains a mystery. Previous work showed that treatment with fosmidomycin, an inhibitor of non-mevalonate isoprenoid precursor biosynthesis in the apicoplast, inhibits the growth of blood-stage P. falciparum. Herein, we demonstrate that fosmidomycin inhibition can be chemically rescued by supplementation with isopentenyl pyrophosphate (IPP), the pathway product. Surprisingly, IPP supplementation also completely reverses death following treatment with antibiotics that cause loss of the apicoplast. We show that antibiotic-treated parasites rescued with IPP over multiple cycles specifically lose their apicoplast genome and fail to process or localize organelle proteins, rendering them functionally apicoplast-minus. Despite the loss of this essential organelle, these apicoplast-minus auxotrophs can be grown indefinitely in asexual blood stage culture but are entirely dependent on exogenous IPP for survival. These findings indicate that isoprenoid precursor biosynthesis is the only essential function of the apicoplast during blood-stage growth. Moreover, apicoplast-minus P. falciparum strains will be a powerful tool for further investigation of apicoplast biology as well as drug and vaccine development.