Lasonder Edwin, Janse Chris J, van Gemert Geert-Jan, Mair Gunnar R, Vermunt Adriaan M W, Douradinha Bruno G, van Noort Vera, Huynen Martijn A, Luty Adrian J F, Kroeze Hans, Khan Shahid M, Sauerwein Robert W, Waters Andrew P, Mann Matthias, Stunnenberg Hendrik G
Department of Molecular Biology, NCMLS, Radboud University Nijmegen, Nijmegen, The Netherlands.
PLoS Pathog. 2008 Oct;4(10):e1000195. doi: 10.1371/journal.ppat.1000195. Epub 2008 Oct 31.
Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from the mosquito -- early and late oocysts containing midgut sporozoites, and the mature, infectious salivary gland sporozoites. Despite the morphological similarity between midgut and salivary gland sporozoites, their proteomes are markedly different, in agreement with their increase in hepatocyte infectivity. The different sporozoite proteomes contain a large number of stage specific proteins whose annotation suggest an involvement in sporozoite maturation, motility, infection of the human host and associated metabolic adjustments. Analyses of proteins identified in the P. falciparum sporozoite proteomes by orthologous gene disruption in the rodent malaria parasite, P. berghei, revealed three previously uncharacterized Plasmodium proteins that appear to be essential for sporozoite development at distinct points of maturation in the mosquito. This study sheds light on the development and maturation of the malaria parasite in an Anopheles mosquito and also identifies proteins that may be essential for sporozoite infectivity to humans.
在按蚊体内发育成熟的恶性疟原虫子孢子会引发人类疟疾感染。在此,我们报告了对来自蚊子的不同寄生虫阶段的首次蛋白质组学比较——含有中肠子孢子的早期和晚期卵囊,以及成熟的、具有感染性的唾液腺子孢子。尽管中肠子孢子和唾液腺子孢子在形态上相似,但它们的蛋白质组明显不同,这与它们对肝细胞感染性的增加相一致。不同的子孢子蛋白质组包含大量阶段特异性蛋白质,其注释表明它们参与子孢子成熟、运动、感染人类宿主以及相关的代谢调整。通过在啮齿动物疟原虫伯氏疟原虫中进行直系同源基因破坏,对在恶性疟原虫子孢子蛋白质组中鉴定出的蛋白质进行分析,揭示了三种以前未被表征的疟原虫蛋白质,它们似乎在蚊子体内成熟的不同阶段对子孢子发育至关重要。这项研究阐明了疟原虫在按蚊体内的发育和成熟过程,还鉴定出了可能对子孢子感染人类至关重要的蛋白质。