Development of a genetic tool for functional screening of anti-malarial bioactive extracts in metagenomic libraries

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Abstract

Background: The chemical treatment of Plasmodium falciparum for human infections is losing efficacy each year due to the rise of resistance. One possible strategy to find novel anti-malarial drugs is to access the largest reservoir of genomic biodiversity source on earth present in metagenomes of environmental microbial communities. Methods: A bioluminescent P. falciparum parasite was used to quickly detect shifts in viability of microcultures grown in 96-well plates. A synthetic gene encoding the Dermaseptin 4 peptide was designed and cloned under tight transcriptional control in a large metagenomic insert context (30 kb) to serve as proof-of-principle for the screening platform. Results: Decrease in parasite viability consistently correlated with bioluminescence emitted from parasite microcultures, after their exposure to bacterial extracts containing a plasmid or fosmid engineered to encode the Dermaseptin 4 anti-malarial peptide. Conclusions: Here, a new technical platform to access the anti-malarial potential in microbial environmental metagenomes has been developed.

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APA

Mongui, A., Pérez-Llanos, F. J., Yamamoto, M. M., Lozano, M., Zambrano, M. M., Del Portillo, P., … Junca, H. (2015). Development of a genetic tool for functional screening of anti-malarial bioactive extracts in metagenomic libraries. Malaria Journal, 14(1). https://doi.org/10.1186/s12936-015-0748-6

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