(圖片來(lái)源:Jennifer Gordon and Wandy Beatty)
生物谷報(bào)道:作為單細(xì)胞的原始生物,,原生動(dòng)物多少有些奇特之處:它們有的像動(dòng)物,有的像植物,,有的兼而有之。美國(guó)科學(xué)家的一項(xiàng)最新研究表明,,一種更像動(dòng)物的原生寄生蟲居然擁有一個(gè)典型的植物生物化學(xué)路徑,。這一結(jié)果有望為抵御由寄生蟲導(dǎo)致的疾病(比如瘧疾)開辟一條新的道路,。相關(guān)論文發(fā)表在1月10日的《自然》雜志上,。
由于原生寄生蟲類似動(dòng)物的生物學(xué)機(jī)制和宿主的十分相似,它們很難被控制,。也正因?yàn)槿绱?,許多針對(duì)這些寄生蟲的藥物往往會(huì)損害患者自身的細(xì)胞。
為了能夠在這一問(wèn)題上取得進(jìn)展,,美國(guó)華盛頓大學(xué)醫(yī)學(xué)院的微生物學(xué)家Kisaburo Nagamune和L. David Sibley領(lǐng)導(dǎo)的研究小組對(duì)一種名為弓形蟲(Toxoplasma gondii,,能夠?qū)е鹿蜗x病)的原生動(dòng)物進(jìn)行了深入研究,。研究人員對(duì)破譯該寄生蟲的溝通機(jī)制尤其感興趣,。
首先,研究人員將從弓形蟲中鑒定出的生化路徑與動(dòng)物體內(nèi)的進(jìn)行了對(duì)比,,以期更好地了解它們的功能,。Sibley說(shuō),“當(dāng)發(fā)現(xiàn)二者之間鮮有相似性時(shí),,我們就意識(shí)到這些原生體可能并非它們看起來(lái)的那樣像動(dòng)物,。”
因此,,研究小組將弓形蟲的信號(hào)路徑又與植物進(jìn)行了對(duì)比,,結(jié)果發(fā)現(xiàn)二者有許多共同點(diǎn),。其中最引人注目的是脫落酸(abscisic acid),一種植物體內(nèi)控制應(yīng)激響應(yīng)和休眠的荷爾蒙,。通常當(dāng)宿主細(xì)胞內(nèi)的弓形蟲達(dá)到一定數(shù)量時(shí),,它們就會(huì)外出肆虐,而當(dāng)研究人員利用一種常用的除草劑阻斷弓形蟲制造脫落酸后,,即使數(shù)量已經(jīng)足夠,,它們?nèi)匀槐3忠环N無(wú)活動(dòng)停滯狀態(tài)。
究其原因,,研究人員認(rèn)為,,應(yīng)該是脫落酸控制著寄生蟲由休眠向活躍的轉(zhuǎn)變,這與植物體內(nèi)的機(jī)制比較相似,。進(jìn)一步的研究發(fā)現(xiàn),,這種除草劑能夠挽救被弓形蟲感染的小鼠。
英國(guó)格拉斯哥大學(xué)的微生物學(xué)家Andy Waters表示,,新的研究創(chuàng)造性地反思了包括變形蟲在內(nèi)的一類寄生蟲,,而對(duì)脫落酸角色的進(jìn)一步的研究有望催生治療瘧疾急需的新方法。(科學(xué)網(wǎng) 任霄鵬/編譯)
生物谷推薦英文原文:
Nature 451, 207-210 (10 January 2008) | doi:10.1038/nature06478; Received 2 October 2007; Accepted 13 November 2007
Abscisic acid controls calcium-dependent egress and development in Toxoplasma gondii
Kisaburo Nagamune1,4, Leslie M. Hicks2, Blima Fux1, Fabien Brossier1,4, Eduardo N. Chini3 & L. David Sibley1
Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA
Donald Danforth Plant Science Center, 975 N. Warson Road, St Louis, Missouri 63132, USA
Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
Present addresses: Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan (K.N.); Linstitut National de la Researche Agronomique, Centre de Recherche de Tours, 37380 Nouzilly, France (F.B.).
Correspondence to: L. David Sibley1 Correspondence and requests for materials should be addressed to L.D.S. (Email: [email protected]).
Abstract
Calcium controls a number of critical events, including motility, secretion, cell invasion and egress by apicomplexan parasites1. Compared to animal2 and plant cells3, the molecular mechanisms that govern calcium signalling in parasites are poorly understood. Here we show that the production of the phytohormone abscisic acid (ABA) controls calcium signalling within the apicomplexan parasite Toxoplasma gondii, an opportunistic human pathogen. In plants, ABA controls a number of important events, including environmental stress responses, embryo development and seed dormancy4, 5. ABA induces production of the second-messenger cyclic ADP ribose (cADPR), which controls release of intracellular calcium stores in plants6. cADPR also controls intracellular calcium release in the protozoan parasite T. gondii 7, 8; however, previous studies have not revealed the molecular basis of this pathway9. We found that addition of exogenous ABA induced formation of cADPR in T. gondii, stimulated calcium-dependent protein secretion, and induced parasite egress from the infected host cell in a density-dependent manner. Production of endogenous ABA within the parasite was confirmed by purification (using high-performance liquid chromatography) and analysis (by gas chromatography-mass spectrometry). Selective disruption of ABA synthesis by the inhibitor fluridone delayed egress and induced development of the slow-growing, dormant cyst stage of the parasite. Thus, ABA-mediated calcium signalling controls the decision between lytic and chronic stage growth, a developmental switch that is central in pathogenesis and transmission. The pathway for ABA production was probably acquired with an algal endosymbiont that was retained as a non-photosynthetic plastid known as the apicoplast. The plant-like nature of this pathway may be exploited therapeutically, as shown by the ability of a specific inhibitor of ABA synthesis to prevent toxoplasmosis in the mouse model.