Research Projects

Salmonella Typhimurium (STM) is an anaerobic bacteria that colonizes in the intestine and other organs of the host organism under microaerobic to anaerobic conditions. The bacteria are regulated by two anaerobic regulators: FNR and ArcA proteins. When one regulator, FNR, is deleted from the bacteria's genome, it results in significant reductions in growth kinetics, swimming motility, biofilm forming ability, and colonization inside mice models. A significant increase in the expression of ethanolamine (EA) metabolism genes, controlled by Ethanolamine utilization transcriptional regulator (EutR), was found in fnr deleted STM compared to wild bacteria. EA is essential for all prokaryotic and eukaryotic cell membranes and can be sourced from food, erosion of gut epithelium, and turnover of gut microbiota. The eut operon contains 17 genes encoding EA metabolism, which are regulated by EutR. To reduce the fitness of bacteria inside macrophages and colonization inside host organs, the researchers plan to target the promoter region of EutR gene of fnr deleted STM and reduce its strength using error-prone PCR or site-directed mutagenesis. However, deletion of EutR may result in total loss of bacterial fitness for colonization and non-immunogenic bacteria. Promoter engineering and deoptimization are new techniques for regulating gene expression, but targeting the promoter will only affect the gene being regulated. Controlling STM infections, particularly in humans, can help reduce gastroenteritis caused by STM, as most STM infections occur due to contaminated poultry eggs and meats.