来自美国约翰霍普金斯大学疟疾研究所的研究人员对在蚊子中肠中常见的一种细菌进行基因改造,发现导致人患上疟疾的疟原虫在携带这种转基因细菌的蚊子体内不能存活。这种被称作成团泛菌(Pantoea agglomerans)的细菌经过基因改造后分泌对疟原虫有毒性的蛋白,但是这种毒素并不伤害蚊子或人。根据2012年7月16日发表在PNAS期刊上的一项最新研究,这种转基因细菌能够有效地减少蚊子体内寄生的疟原虫,而且有效率为98%。
论文通讯作者、约翰霍普金斯大学布隆伯格公共卫生学院(Johns Hopkins Bloomberg School of Public Health)教授Marcelo Jacobs-Lorena博士说,“在过去,我们努力开发转基因蚊子来抵抗疟疾,但是开发转基因细菌是一种更为简单的方法。这项研究的最终目标就是完全阻止蚊子传播疟原虫来感染人类。”
在这项研究中,Jacobs-Lorena和他的同事们发现经过基因改造的成团泛菌菌株抑制最为致命性的人疟原虫---即恶性疟原虫(Plasmodium falciparum)---和啮齿类动物疟原虫---即伯氏鼠疟原虫(Plasmodium berghei)---生长。在携带这种转基因细菌的蚊子体内,抑制率高达98%,而且携带疟原虫的蚊子比例下降高达84%。
Jacobs-Lorena说,“我们证实利用转基因共生细菌来干扰蚊子体内恶性疟原虫的生长。这些发现为利用转基因共生细菌作为一种强大的工具来对抗疟疾奠定基础。”(生物谷:Bioon.com)
本文编译自Genetically engineered bacteria prevent mosquitoes from transmitting malaria
doi:10.1073/pnas.1204158109
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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.