Establishment of a Novel Whole Animal HTS Technology Platform for Melioidosis Drug Discovery

Author(s): Umayal Lakshmanan, Amelia Yap, Justina Fulwood, Li Yichun, Sim Siew Hoon, Jolander Lim, Audrey Ting, Xiao Hui Sem, Jason F. Kreisberg, Patrick Tan, Gladys Tan, Horst Flotow

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 17 , Issue 9 , 2014

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Melioidosis is a serious emerging endemic infectious disease caused by Burkholderia pseudomallei, a gramnegative 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.

Keywords: C. elegans, HTS, Melioidosis drug discovery, whole animal screening.

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Article Details

Year: 2014
Published on: 19 October, 2014
Page: [790 - 803]
Pages: 14
DOI: 10.2174/1386207317666141019195031
Price: $65

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