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Development of a genetic tool for functional screening of anti-malarial bioactive extracts in metagenomic libraries
Mongui, A.; Pérez-Llanos, F. J.; Yamamoto, M. M.; Lozano Molero, Miguel; Zambrano, M.M.; Portillo Obando, Hernando A. del; Fernández Becerra, Carmen; Restrepo, S.; Junca, H.
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.
Genòmica
Genètica microbiana
Malària
Plasmodium falciparum
Resistència als medicaments
Efecte dels medicaments sobre els microorganismes
Genomics
Microbial genetics
Malaria
Plasmodium falciparum
Drug resistance
Effect of drugs on microorganisms
cc by (c) Mongui et al., 2015
http://creativecommons.org/licenses/by/3.0/es/
Artículo
info:eu-repo/semantics/publishedVersion
BioMed Central
         

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