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

Autor: Mongui A; RG Microbial Ecology: Metabolism, Genomics & Evolution - CorpoGen, Bogotá, Colombia. amonguic@gmail.com.; Department of Biological Sciences, Universidad de los Andes, Bogotá, Colombia. amonguic@gmail.com., Pérez-Llanos FJ; RG Microbial Ecology: Metabolism, Genomics & Evolution - CorpoGen, Bogotá, Colombia. francisjpll@gmail.com.; Department of Biological Sciences, Universidad de los Andes, Bogotá, Colombia. francisjpll@gmail.com., Yamamoto MM; Departamento de Parasitologia, Universidade de São Paulo, São Paulo, Brazil. masayama@gmail.com., Lozano M; RG Microbial Ecology: Metabolism, Genomics & Evolution - CorpoGen, Bogotá, Colombia. macheperez@hotmail.com., Zambrano MM; RG Microbial Ecology: Metabolism, Genomics & Evolution - CorpoGen, Bogotá, Colombia. mzambrano@corpogen.org., Del Portillo P; RG Microbial Ecology: Metabolism, Genomics & Evolution - CorpoGen, Bogotá, Colombia. pdelportillo@corpogen.org., Fernández-Becerra C; ICREA at ISGlobal, Barcelona Ctr Int Health Res (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain. carmen.fernandez@cresib.cat., Restrepo S; Department of Biological Sciences, Universidad de los Andes, Bogotá, Colombia. srestrep@uniandes.edu.co., Del Portillo HA; ICREA at ISGlobal, Barcelona Ctr Int Health Res (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain. hernandoa.delportillo@cresib.cat.; Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain. hernandoa.delportillo@cresib.cat., Junca H; RG Microbial Ecology: Metabolism, Genomics & Evolution - CorpoGen, Bogotá, Colombia. info@howardjunca.com.; Present Address: Applied Biology Program, Faculty of Basic & Applied Sciences, Universidad Militar Nueva Granada-UMNG, Campus Cajicá, Bogotá, DC, Colombia. info@howardjunca.com.
Jazyk: angličtina
Zdroj: Malaria journal [Malar J] 2015 Jun 04; Vol. 14, pp. 233. Date of Electronic Publication: 2015 Jun 04.
DOI: 10.1186/s12936-015-0748-6
Abstrakt: 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.
Databáze: MEDLINE