來自美國約翰霍普金斯大學(xué)瘧疾研究所的研究人員對在蚊子中腸中常見的一種細(xì)菌進(jìn)行基因改造，發(fā)現(xiàn)導(dǎo)致人患上瘧疾的瘧原蟲在攜帶這種轉(zhuǎn)基因細(xì)菌的蚊子體內(nèi)不能存活,。這種被稱作成團(tuán)泛菌(Pantoea agglomerans)的細(xì)菌經(jīng)過基因改造后分泌對瘧原蟲有毒性的蛋白,，但是這種毒素并不傷害蚊子或人。根據(jù)2012年7月16日發(fā)表在PNAS期刊上的一項(xiàng)最新研究，這種轉(zhuǎn)基因細(xì)菌能夠有效地減少蚊子體內(nèi)寄生的瘧原蟲,，而且有效率為98%,。
論文通訊作者、約翰霍普金斯大學(xué)布隆伯格公共衛(wèi)生學(xué)院(Johns Hopkins Bloomberg School of Public Health)教授Marcelo Jacobs-Lorena博士說,，“在過去,，我們努力開發(fā)轉(zhuǎn)基因蚊子來抵抗瘧疾，但是開發(fā)轉(zhuǎn)基因細(xì)菌是一種更為簡單的方法,。這項(xiàng)研究的最終目標(biāo)就是完全阻止蚊子傳播瘧原蟲來感染人類,。”
在這項(xiàng)研究中，Jacobs-Lorena和他的同事們發(fā)現(xiàn)經(jīng)過基因改造的成團(tuán)泛菌菌株抑制最為致命性的人瘧原蟲---即惡性瘧原蟲(Plasmodium falciparum)---和嚙齒類動物瘧原蟲---即伯氏鼠瘧原蟲(Plasmodium berghei)---生長,。在攜帶這種轉(zhuǎn)基因細(xì)菌的蚊子體內(nèi),，抑制率高達(dá)98%，而且攜帶瘧原蟲的蚊子比例下降高達(dá)84%,。
Jacobs-Lorena說,，“我們證實(shí)利用轉(zhuǎn)基因共生細(xì)菌來干擾蚊子體內(nèi)惡性瘧原蟲的生長。這些發(fā)現(xiàn)為利用轉(zhuǎn)基因共生細(xì)菌作為一種強(qiáng)大的工具來對抗瘧疾奠定基礎(chǔ),。”(生物谷：Bioon.com)
本文編譯自Genetically engineered bacteria prevent mosquitoes from transmitting malaria
doi:10.1073/pnas.1204158109
PMC:
PMID:
Fighting malaria with engineered symbiotic bacteria from vector mosquitoes
Sibao Wanga, Anil K. Ghosha, Nicholas Bongiob, Kevin A. Stebbingsb,1, David J. Lampeb, and Marcelo Jacobs-Lorenaa,2
The most vulnerable stages of Plasmodium development occur in the lumen of the mosquito midgut, a compartment shared with symbiotic bacteria. Here, we describe a strategy that uses symbiotic bacteria to deliver antimalaria effector molecules to the midgut lumen, thus rendering host mosquitoes refractory to malaria infection. The Escherichia coli hemolysin A secretion system was used to promote the secretion of a variety of anti-Plasmodium effector proteins by Pantoea agglomerans, a common mosquito symbiotic bacterium. These engineered P. agglomerans strains inhibited development of the human malaria parasite Plasmodium falciparum and rodent malaria parasite Plasmodium berghei by up to 98%. Significantly, the proportion of mosquitoes carrying parasites (prevalence) decreased by up to 84% for two of the effector molecules, scorpine, a potent antiplasmodial peptide and (EPIP)4, four copies of Plasmodium enolase–plasminogen interaction peptide that prevents plasminogen binding to the ookinete surface. We demonstrate the use of an engineered symbiotic bacterium to interfere with the development of P. falciparum in the mosquito. These findings provide the foundation for the use of genetically modified symbiotic bacteria as a powerful tool to combat malaria.
