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Combining transgenesis with paratransgenesis to fight malaria

Malaria is among the deadliest infectious diseases, and Plasmodium, the causative agent, needs to complete a complex development cycle in its vector mosquito for transmission to occur. Two promising strategies to curb transmission are transgenesis, consisting of genetically engineering mosquitoes to...

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Autores principales: Huang, Wei, Vega-Rodriguez, Joel, Kizito, Chritopher, Cha, Sung-Jae, Jacobs-Lorena, Marcelo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596157/
https://www.ncbi.nlm.nih.gov/pubmed/36281969
http://dx.doi.org/10.7554/eLife.77584
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author Huang, Wei
Vega-Rodriguez, Joel
Kizito, Chritopher
Cha, Sung-Jae
Jacobs-Lorena, Marcelo
author_facet Huang, Wei
Vega-Rodriguez, Joel
Kizito, Chritopher
Cha, Sung-Jae
Jacobs-Lorena, Marcelo
author_sort Huang, Wei
collection PubMed
description Malaria is among the deadliest infectious diseases, and Plasmodium, the causative agent, needs to complete a complex development cycle in its vector mosquito for transmission to occur. Two promising strategies to curb transmission are transgenesis, consisting of genetically engineering mosquitoes to express antimalarial effector molecules, and paratransgenesis, consisting of introducing into the mosquito commensal bacteria engineered to express antimalarial effector molecules. Although both approaches restrict parasite development in the mosquito, it is not known how their effectiveness compares. Here we provide an in-depth assessment of transgenesis and paratransgenesis and evaluate the combination of the two approaches. Using the Q-system to drive gene expression, we engineered mosquitoes to produce and secrete two effectors – scorpine and the MP2 peptide – into the mosquito gut and salivary glands. We also engineered Serratia, a commensal bacterium capable of spreading through mosquito populations to secrete effectors into the mosquito gut. Whereas both mosquito-based and bacteria-based approaches strongly reduced the oocyst and sporozoite intensity, a substantially stronger reduction of Plasmodium falciparum development was achieved when transgenesis and paratransgenesis were combined. Most importantly, transmission of Plasmodium berghei from infected to naïve mice was maximally inhibited by the combination of the two approaches. Combining these two strategies promises to become a powerful approach to combat malaria.
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spelling pubmed-95961572022-10-26 Combining transgenesis with paratransgenesis to fight malaria Huang, Wei Vega-Rodriguez, Joel Kizito, Chritopher Cha, Sung-Jae Jacobs-Lorena, Marcelo eLife Microbiology and Infectious Disease Malaria is among the deadliest infectious diseases, and Plasmodium, the causative agent, needs to complete a complex development cycle in its vector mosquito for transmission to occur. Two promising strategies to curb transmission are transgenesis, consisting of genetically engineering mosquitoes to express antimalarial effector molecules, and paratransgenesis, consisting of introducing into the mosquito commensal bacteria engineered to express antimalarial effector molecules. Although both approaches restrict parasite development in the mosquito, it is not known how their effectiveness compares. Here we provide an in-depth assessment of transgenesis and paratransgenesis and evaluate the combination of the two approaches. Using the Q-system to drive gene expression, we engineered mosquitoes to produce and secrete two effectors – scorpine and the MP2 peptide – into the mosquito gut and salivary glands. We also engineered Serratia, a commensal bacterium capable of spreading through mosquito populations to secrete effectors into the mosquito gut. Whereas both mosquito-based and bacteria-based approaches strongly reduced the oocyst and sporozoite intensity, a substantially stronger reduction of Plasmodium falciparum development was achieved when transgenesis and paratransgenesis were combined. Most importantly, transmission of Plasmodium berghei from infected to naïve mice was maximally inhibited by the combination of the two approaches. Combining these two strategies promises to become a powerful approach to combat malaria. eLife Sciences Publications, Ltd 2022-10-25 /pmc/articles/PMC9596157/ /pubmed/36281969 http://dx.doi.org/10.7554/eLife.77584 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (https://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Microbiology and Infectious Disease
Huang, Wei
Vega-Rodriguez, Joel
Kizito, Chritopher
Cha, Sung-Jae
Jacobs-Lorena, Marcelo
Combining transgenesis with paratransgenesis to fight malaria
title Combining transgenesis with paratransgenesis to fight malaria
title_full Combining transgenesis with paratransgenesis to fight malaria
title_fullStr Combining transgenesis with paratransgenesis to fight malaria
title_full_unstemmed Combining transgenesis with paratransgenesis to fight malaria
title_short Combining transgenesis with paratransgenesis to fight malaria
title_sort combining transgenesis with paratransgenesis to fight malaria
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596157/
https://www.ncbi.nlm.nih.gov/pubmed/36281969
http://dx.doi.org/10.7554/eLife.77584
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