Bacteria-Derived Natural Compounds Ameliorating Lipopolysaccharide Induced Acute Lung Injury

The main objective of this project is, based on the current knowledge of Serratia marcescens physiology and metabolism, to unravel novel cellular metabolite molecules involved in bacterial cell-to-mammalian host interaction and to understand the underlying biochemical mechanisms in the opportunistic pathogen S. marcescens. Potential compounds from other bacteria will also be incorporated. Our preliminary studies have clearly shown that one of the chemical molecules 2, 3-butanediol represses mammalian pro-inflammatory responses in a rat model of lipopolysaccharide (LPS) (produced by S. marcescens) induced acute lung injury (ALI). Such an efficacy is comparable to that of the polyphenol compound resveratrol. The effect is further identified to act through modulation of the NF-κB signaling pathway, including inhibition of IκB phosphorylation and the subsequent NF-κB activation. Besides 2, 3-butanediol, many other compounds also showed clear immuno-modulatory effect against the host. These data suggested S. marcescens might use some uncharacterized effector compounds for evading attack from the host. How the metabolite compounds modulate the host immune response will be further characterized in detail. These results suggest that 2,3-butanediol bears great potential in the development of anti-inflammatory drug for prevention of LPS-induced ALI. This study will help us understand the pathogenesis of S. marcescens infection, and furthermore, unravel novel mechanisms of interaction between pathogens and the host.

Project ID:PC9609-3795
External Project ID:NSC96-2628-B182-033-MY3