Virulence of E. coli influenced by environmental signals

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Escherichia coli pathogens often cycle between host dependent and host-independent lifestyles. Thus, they must adapt to changing environments and respond to different environmental cues. To endure the frequent changes in nutrient availability, bacteria possess an arsenal of regulatory and metabolic genes allowing rapid adaptation and high flexibility.  Using a pathogenic E. coli model, we are exploring the potential cross-talk between virulence and two types of bacterial metabolic responses:   a) The animal gut environment contains a rich diversity of nutrients, coming in part from the symbiotic relationships established by the microbiota. Using functional genomics, we observed an important shift in the expression of metabolic and virulence genes in pathogenic intestinal E. coli in the presence of metabolites from the gut microbiota.  We are deciphering the mechanistic details of the regulatory systems by which signals from the intestinal microbiota environment influence E. coli virulence.   b) Bacterial pathogens, including those of humans, animals, and plants, encounter phosphate (Pi)-limiting or Pi-rich environments. The phosphate (Pi)-concentration modulates the expression of the Pho regulon, which is controlled in part by the PhoB/PhoR, a two component regulatory system (TCRS). This TCRS allows bacteria to regulate phosphate assimilation pathways accordingly. Under Pi-limiting conditions, E. coli uses the transcriptional-response regulator PhoB to translate the Pi starvation signal sensed by the bacterium into gene activation or repression. We are exploring how the Pi signal is not only employed for the maintenance of bacterial Pi homeostasis but also to regulate virulence traits, including the formation of biofilm.   This work will greatly improve our knowledge on the adaptive response of pathogenic Escherichia coli to defined environment such as the gut and Pi-depleted environments. The novelty resides in a better understanding of the links between bacterial metabolism and E. coli virulence. This is important for the development of future therapeutic and prophylactic strategies against bacterial pathogens and especially relevant in animal rearing conditions.