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.