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

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 en...

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Bibliographic Details
Authors: Mongui, Alvaro, Pérez-Llanos, Francy J., Yamamoto, Marcio M., Lozano, Marcela, Zambrano, Maria M., Portillo, Patricis Del, Fernández Becerra, María del Carmen, Restrepo, Silvia, Junca, Howard
Format: article
Status:Published version
Publication Date:2015
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/69246
Online Access:https://hdl.handle.net/2445/69246
Access Level:Open access
Keyword:Genòmica
Genètica microbiana
Malària
Plasmodium falciparum
Resistència als medicaments
Efecte dels medicaments sobre els microorganismes
Genomics
Microbial genetics
Malaria
Drug resistance
Effect of drugs on microorganisms
Description
Summary: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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