Uropathogenic Echerichia coli (UPEC) are a leading cause of community-acquired urinary tract infections (UTI). UTIs can be a recurrent infection, originating from the fact that the bacterial colonies can persevere clearance and then reestablish infection as they multiply. One method by which these bacteria are protected from clearance is the formation of bacterial colonies encapsulated with proteins and polysaccharides – termed biofilms. Biofilms promote longevity through protection from oxidative stress as well as oxygen deprivation. Additionally, in a biofilm, only a portion of the community is exposed to endogenous response elements at any one time. One of the main constituents of these biofilms is the amyloid protein curli. Making up 85% of the E. coli extracellular matrix, curli represents a potential inhibition target in biofilm formation. Additionally, inhibitors of this in vivo, functional amyloid can help in our understanding of amyloid formation by other proteins. Using transmission electron microscopy (TEM), absorbance and fluorescence spectroscopy, in vitro polymerization assays, and western blotting we discovered that a small molecule inhibitor, nordihydroguaiaretic acid (NDGA), is a potent inhibitor of curli formation. Additionally, biofilm formation at the solid-air and liquid-air interfaces in the presence of drug was drastically affected with changes in physical integrity. Surprisingly, while treatment with compound appears to shorten curli amyloid fibers there is an apparent increase in liquid-air biofilm integrity that drops off at higher concentrations. NDGA, derived from the creosote bush, has been already been shown to have antioxidant activity, but its anti-bacterial effects have not been explored.This work provides the potential for this previously characterized compound to be used as a therapeutic to alleviate the symptoms and effects of UTIs.

Potent small molecule curli inhibitor in UPEC that alters biofilm formation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.