ABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Burkholderia pseudomallei/drug effects , Drug Discovery , High-Throughput Screening Assays , Melioidosis/drug therapy , Small Molecule Libraries/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/microbiology , Disease Models, Animal , Melioidosis/microbiology , Small Molecule Libraries/chemistryABSTRACT
To assay the quantity of the brucine ingredient in gastric content and hepatic tissues from the patient died of Semen Strychni hainanensi accumulative posioning.With standard brucine and the crude powder of the Semen Strychni hainanensi as control,the brucine ingredients in the above tissues were quantitatively scanned by the capillary elecrophoretic apparatus within the wave length ranging 190～600nm.The contents of the brucine ingredients in the gastric,hepatic tissues and the crude powder of the Semen Strychni sainanensi were 5 83mg/100ml,4 92mg/100g,and 3 07%(w/w)respectively.The high level of the brucine ingredients in the gastric content and the hepatic tissue is the cause of death.
