3 research outputs found
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 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
Development of a genetic tool for functional screening of anti-malarial bioactive extracts in metagenomic libraries
Ajuts: Departamento Administrativo de Ciencias, Tecnología e Innovación (Colciencias), República de Colombia; Convocatoria 489 - 2009, Código 657048925406, Contrato de financiación RC. 427 - 2009 Colciencias - CorpoGen; Programa de Asistencias Graduadas de Universidad de los Andes, Bogotá, Colombia; i Programa Jóvenes Investigadores de ColcienciasBACKGROUND: 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. Here, a new technical platform to access the anti-malarial potential in microbial environmental metagenomes has been develope
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 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