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

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...

Full description

Saved in:
Bibliographic Details
Published in:Malaria journal 2015-06, Vol.14 (1), p.233-233, Article 233
Main Authors: Mongui, Alvaro, Pérez-Llanos, Francy J, Yamamoto, Marcio M, Lozano, Marcela, Zambrano, Maria M, Del Portillo, Patricia, Fernández-Becerra, Carmen, Restrepo, Silvia, Del Portillo, Hernando A, Junca, Howard
Format: Article
Language:English
Subjects:
Antimalarials - pharmacology
Biodiversity
Drug resistance
Efecte dels medicaments sobre els microorganismes
Effect of drugs on microorganisms
Genomic Library
Genomics
Genètica microbiana
Genòmica
Malaria
Malaria, Falciparum - drug therapy
Malària
Metagenome
Methodology
Microbial genetics
Parasitic Sensitivity Tests
Plant Extracts - pharmacology
Plants - chemistry
Plasmodium falciparum
Plasmodium falciparum - drug effects
Plasmodium falciparum - genetics
Resistència als medicaments
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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. Here, a new technical platform to access the anti-malarial potential in microbial environmental metagenomes has been developed.
ISSN:1475-2875
1475-2875
DOI:10.1186/s12936-015-0748-6