TY - JOUR
T1 - Driving mosquito refractoriness to Plasmodium falciparum with engineered symbiotic bacteria
AU - Wang, Sibao
AU - Dos-Santos, André L.A.
AU - Huang, Wei
AU - Liu, Kun
AU - Oshaghi, Mohammad Ali
AU - Wei, Ge
AU - Agre, Peter
AU - Jacobs-Lorena, Marcelo
N1 - Funding Information:
We thank R. Smith for collecting mosquito hemolymph samples. This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (grant XDB11010500), the National Natural Science Foundation of China (grant 31472044), the One Hundred Talents Program of the Chinese Academy of Sciences (grant 2013OHTP01), and the U.S. National Institute of Allergy and Infectious Diseases (grant AI 031478). A.L.A.D.-S. was supported by a grant from the Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnológico Science Without Borders program (process number 245456/2012-0). We thank the Johns Hopkins Malaria Research Institute’s mosquito and P. falciparum core facilities for help with mosquito rearing and parasite cultures. Additional support was provided by the Johns Hopkins Malaria Research Institute and the Bloomberg Philanthropies. The supply of human blood was supported by U.S. National Institutes of Health grant RR00052. S.W. and M.J.-L. conceived and designed the experiments. S.W. performed the majority of experiments. M.A.O. and K.C.L. conducted Western blot analysis and transmission-blocking assays. W.H. and M.A.O. performed the cage experiments and tested the blood-feeding effect. G.W. generated fluorescent bacteria and conducted morphology and phylogenetic analysis. S.W., A.L.A.D.-S., W.H., K.C.L., M.A.O., P.A., and M.J.-L. analyzed the data. S.W. and M.J.-L. wrote the manuscript. All the data and code needed to understand and assess the conclusions of this research are available in the main text, supplementary materials, and GenBank (accession number KY935421).
Publisher Copyright:
© 2017, American Association for the Advancement of Science. All rights reserved.
PY - 2017/9/29
Y1 - 2017/9/29
N2 - The huge burden of malaria in developing countries urgently demands the development of novel approaches to fight this deadly disease. Although engineered symbiotic bacteria have been shown to render mosquitoes resistant to the parasite, the challenge remains to effectively introduce such bacteria into mosquito populations. We describe a Serratia bacterium strain (AS1) isolated from Anopheles ovaries that stably colonizes the mosquito midgut, female ovaries, and male accessory glands and spreads rapidly throughout mosquito populations. Serratia AS1 was genetically engineered for secretion of anti-Plasmodium effector proteins, and the recombinant strains inhibit development of Plasmodium falciparum in mosquitoes.
AB - The huge burden of malaria in developing countries urgently demands the development of novel approaches to fight this deadly disease. Although engineered symbiotic bacteria have been shown to render mosquitoes resistant to the parasite, the challenge remains to effectively introduce such bacteria into mosquito populations. We describe a Serratia bacterium strain (AS1) isolated from Anopheles ovaries that stably colonizes the mosquito midgut, female ovaries, and male accessory glands and spreads rapidly throughout mosquito populations. Serratia AS1 was genetically engineered for secretion of anti-Plasmodium effector proteins, and the recombinant strains inhibit development of Plasmodium falciparum in mosquitoes.
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U2 - 10.1126/science.aan5478
DO - 10.1126/science.aan5478
M3 - Article
C2 - 28963255
AN - SCOPUS:85030125023
SN - 0036-8075
VL - 357
SP - 1399
EP - 1402
JO - Science
JF - Science
IS - 6358
ER -