Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhoea in young children and travellers in developing countries, leading to severe morbidity and mortality. It is estimated that many thousands of deaths annually, as well as countless episodes of diarrhoea, are attributable to ETEC. To cause disease, ETEC must first adhere to the small intestine, using one or more colonisation factors (CFs), and then deliver either or both of two toxins, the heat-stable and heat-labile enterotoxins. CFs are immunogenic, and have been a popular vaccine target. However, strains of ETEC display a wide variety of CFs, making the production of a widely protective CF-based vaccine problematic.
While the genes encoding the structural subunits of the CFs are diverse, a large proportion of CFs are transcriptionally controlled by a conserved AraC-like regulator, known as Rns. Being absolutely required for effective production of many CFs, Rns is an attractive drug target. However, little is known about which genes may be under Rns control. In order to identify other potential gene targets of Rns, mRNA-sequencing was performed on ETEC strain H10407. Additionally, we are screening a library of chemical compounds for inhibitors of Rns function, with the aim of identifying a suitable drug to prevent ETEC-induced diarrhoea by disrupting CF production. High-throughput screening has identified multiple hit compounds which are currently under investigation as potential virulence inhibitors.