Selective Antagonism of IBD Associated Dysbiotic Bacteria

Principal Investigator: Kenneth W. Simpson

Department of Clinical Sciences
Sponsor: Weill Cornell Medical College (NIH)
Grant Number: 1 UL1 TR002384-01
Title: Selective Antagonism of IBD Associated Dysbiotic Bacteria
Project Amount: $12,500
Project Period: November 2017 to June 2018

DESCRIPTION (provided by applicant): 

In previous studies we determined that pathways related to the metabolism of ethanolamine and propanediol are involved in the growth and virulence of IBD associated Adherent and Invasive E.coli (AIEC). Comparative genomic analysis revealed these pathways are shared by other dysbiotic bacteria, including Enterococcus, Salmonella, Shigella and Clostridium difficile. In silico modeling in E.coli yielded a panel of candidate small molecules designed to target enzymes involved in ethanolamine and propanediol metabolism. In vitro evaluation of 4 of these boric and boronic acid compounds shows they inhibit growth of AIEC and E. faecalis in defined and complex media, and adhesion and invasion of cultured cells. Moreover these compounds also inhibit AIEC motility, FimH mediated binding and virulence gene expression, and NF-kB induction in epithelial cells. These compounds are non-genotoxic and low in cytotoxicity to the cell lines we have utilized. They are bacteriostatic rather than bacteriocidal. These findings suggest that small boron-containing molecules may be viable candidates for therapeutic intervention against dysbiosis-associated intestinal inflammation.