Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Intestinal infections with Escherichia coli are a major cause of morbidity and mortality in pigs. A distinctive variety of Shiga toxin-producing E. coli (STEC) is responsible for outbreaks of oedema disease (OD), causing significant losses to the pig industry worldwide. Key virulence factors of the causative strain include Shiga toxin 2e (Stx2e) and F18 colonisation fimbriae which mediate STEC adherence to the small intestine. The genes encoding F18 are organised in a single operon (fedABCEF). Our preliminary data show that FedR is a master virulence-regulator that strongly upregulates the expression of the F18 operon as well as its own expression. The high level of activation induced by FedR suggests that inhibiting FedR will block F18-mediated colonisation and prevent OD. In this project, we will screen a small compound library to identify inhibitors that specifically target FedR and assess the effect of these compounds on colonisation and infection using our well-established in vitro and in vivo systems. Identification of a synthetic antimicrobial that inhibits STEC adherence to pig intestine will have a dual-benefit of alleviating the impact of OD on the pig industry whilst addressing antibiotic resistance within porcine STEC strains.