On the trail of EHEC/EAEC--unraveling the gene regulatory networks of human pathogenic Escherichia coli bacteria

Pathogenic Escherichia coli, such as Enterohemorrhagic E. coli (EHEC) and Enteroaggregative E. coli (EAEC), are globally widespread bacteria. Some may cause the hemolytic uremic syndrome (HUS). Varying strains cause epidemics all over the world. Recently, we observed an epidemic outbreak of a multi-resistant EHEC strain in Western Europe, mainly in Germany. The Robert Koch Institute reports >4300 infections and >50 deaths (July, 2011). Farmers lost several million EUR since the origin of infection was unclear. Here, we contribute to the currently ongoing research with a computer-aided study of EHEC transcriptional regulatory interactions, a network of genetic switches that control, for instance, pathogenicity, survival and reproduction of bacterial cells. Our strategy is to utilize knowledge of gene regulatory networks from the evolutionary relative E. coli K-12, a harmless strain mainly used for wet lab studies. In order to provide high-potential candidates for human pathogenic E. coli bacteria, such as EHEC, we developed the integrated online database and an analysis platform EhecRegNet. We utilize 3489 known regulations from E. coli K-12 for predictions of yet unknown gene regulatory interactions in 16 human pathogens. For these strains we predict 40,913 regulatory interactions. EhecRegNet is based on the identification of evolutionarily conserved regulatory sites within the DNA of the harmless E. coli K-12 and the pathogens. Identifying and characterizing EHEC's genetic control mechanism network on a large scale will allow for a better understanding of its survival and infection strategies. This will support the development of urgently needed new treatments. EhecRegNet is online via http://www.ehecregnet.de.