Environmentally Relevant Responses in Different Escherichia Coli Pathotypes: A Functional Genomics Study of Motility and Associated Regulons

Known genome sequences of multiple E. coli pathotypes are a unique resource for investigation of gene regulation in biologically distinctive relatives, by the powerful methods of functional genomics. We will compare a carefully selected set of pathotypes using phenotypic and functional genomics methods, focusing on regulons significant in environmental survival and persistence. <P>
We will thus comprehend the diversity of function of transcription networks within 'wild' members of the species, and gain a clear view of the relevance of the K-12 lab model as a paradigm for the species as a whole. Among less investigated transcription networks relevant to survival in nature is the FlhDC regulon, named for its control of motility but increasingly implicated in other cellular responses, for example to metals such as copper and to oxidative stress, through cross talk with the Fur and SoxS regulons among others. It is also a key target for modulation by the cellular signal molecule cyclic-di-GMP. This signal is intimately involved in the transition from planktonic phenotypes (swimming) to biofilm (non-flagellar e.g. twitching motility) in many bacteria including wild-type E. coli, a phenomenon also favoured at ambient temperatures.<P> We propose that FlhDC and associated regulons have a key role in less explored aspects of adaptation of diverse wild E. coli pathotypes to their natural environments. We will define both the broad phenotype, using Biolog phenotypic arrays, and the FlhDC, Fur and SoxS regulons, in selected pathotypes (ETEC, EHEC, UPEC) representing the breadth of the species and in K-12, both by conventional transcriptomics and by ChIP-on-chip analysis. We will analyse and compare global gene expression in wild types and mutants in these transcription factors, with and without exposure to cognate stimuli. <P>Thus we will advance understanding of the regulation of motility and related behaviours of E. coli in nature.