Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.05.326769v1?rss=1 Authors: Midgett, C. R., Talbot, K. M., Day, J. L., Munson, G. P., Kull, F. J. Abstract: Infections caused by the gram-negative bacteria enterotoxigenic Escherichia coli (ETEC), Vibrio cholerae, Shigella flexneri, and Salmonella enterica are among the most common enteric pathogens and infect billions of people each year. These bacteria control expression of virulence factors using a genetic network of transcriptional regulators, some of which are modulated by small molecules as has been shown for ToxT, an AraC family member from V. cholerae. In ETEC the expression of many types of adhesive pili is dependent upon the AraC family member Rns. We present here the 3 [A] crystal structure of Rns and show it closely resembles ToxT. Furthermore, Rns contains a ligand, decanoic acid, that inhibits its activity in a manner similar to the fatty acid mediated inhibition observed for ToxT and the S. enterica homologue HilD. Rns crystallized as a dimer via an interface similar to that observed in other dimeric AraC's. Together, these results support our hypothesis that virulence controlling AraC family members are regulated by fatty acids in a common manner in a number of enteric pathogens. Furthermore, for the first time this work identifies a small molecule capable of inhibiting ETEC virulence, providing a basis for development of therapeutics against this deadly human pathogen. Copy rights belong to original authors. Visit the link for more info