Functional genomics and systems-level analysis of septicemic E. coli pathogens

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Virulent ExPEC (Extraintestinal Pathogenic Escherichia coli) strains have emerged as a majorcause of bacterial septicemia, both in community and hospital -acquired disease. This pathogenis a predominant cause of death from infectious diseases among older and immuno-suppressedpeople, Colisepticemia (colibacillosis) is complicated by the abundance of drug resistance andthe broad variety of E. coli serotypes.To cause sepsis, bacteria have to survive in serum, which is highly bactericidal for E. coli.Surprisingly, the molecular basis of serum resistance in E. coli and other Gram negativebacteria is poorly understood. Here we propose to use functional genomics tools - deep RNAsequencing, proteomics and bioinformatics in order to characterize the ExPEC genes involvedin response to serum and their expression. These genes will be further studied by determiningtheir abundance among invasive strains, the genetic and environmental regulation of theirexpression, and their role in sepsis and pathogenesis. The results will provide a global,systematic outlook on the mechanisms utilized by ExPEC to promote serum survival andsepticemia. These data will further our understanding of life-threatening blood infections andidentify new potential targets which will help to design vaccines and pathogen-specific antibacterialagents. Thus, we expect that this project will be instrumental in the development of alternative strategies for the detection and prevention of these important newly-emerging infections.