Establishment of a novel whole animal HTS technology platform for melioidosis drug discovery.
Comb Chem High Throughput Screen
; 17(9): 790-803, 2014.
Article
en En
| MEDLINE
| ID: mdl-25329838
Melioidosis is a serious emerging endemic infectious disease caused by Burkholderia pseudomallei, a gram-negative pathogen. Septicemic melioidosis has a mortality rate of 50% even with treatment. Like other gram-negative bacteria, B. pseudomallei is resistant to a number of antibiotics and multi-drug resistant B. pseudomallei is beginning to be encountered in hospitals. There is a clear medical need to develop new treatment options to manage this disease. We used Burkholderia thailandensis (a BSL-2 class organism) to infect Caenorhabditis elegans and set up a surrogate whole animal infection model of melioidosis that we could run in a 384 microtitre plate and establish a whole animal HTS assay. We have optimized and validated this assay in a fluorescence-based format that can be run on our automated screening platforms. This assay has now been used to screen over 300,000 compounds from our small molecule library and we are in the process of characterizing the hits obtained and select compounds for further studies. We have thus established a biologically relevant assay technology platform to screen for antibacterial compounds and used this platform to identify new compounds that may find application in treating melioidosis infections.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Burkholderia pseudomallei
/
Bibliotecas de Moléculas Pequeñas
/
Descubrimiento de Drogas
/
Ensayos Analíticos de Alto Rendimiento
/
Melioidosis
/
Antibacterianos
Límite:
Animals
Idioma:
En
Revista:
Comb Chem High Throughput Screen
Asunto de la revista:
BIOLOGIA MOLECULAR
/
QUIMICA
Año:
2014
Tipo del documento:
Article
Pais de publicación:
Emiratos Árabes Unidos