Development of an HTS system to identify natural chemicals that specifically inhibit Escherichia coli O157:H7 adhesion to host cells

Adhesion to intestinal epithelium is critical for virulence and infection of Escherichia coli O157:H7, which is a major cause of foodborne illnesses. Targeting adhesion but not growth of the pathogen is an effective approach to control bacterial infections. In this study, a high-throughput screening system was developed to identify anti-adhesive natural chemicals using a reporter strain whose activity entirely depends on Ler since genes encoding the locus of enterocyte effacement (LEE) which forms attaching and effacing lesions are known to be activated by Ler. A selected hit, yomogin, suppressed the expression of virulent genes encoded within the LEE without affecting bacterial growth itself. Yomogin significantly reduced the adherence of E. coli O157:H7 to Caco-2 epithelial cells and cytotoxicity. These results indicated that the developed system allows for rapid and cost-effective discovery of novel anti-adhesive agents and yomogin can prevent early stage of E. coli O157:H7 pathogenesis.