E. coli niche expansion and adaptation in the dysbiotic intestine

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The research in this proposal will explore the genetic components that enable commensal E. coli to expand their niche in the context of intestinal dysbiosis associated with inflammation. The work will take advantage of a new E. coli commensal colonization model in mice that allows the growth of competing flora, and will focus on genes that are not required for colonization of healthy mice. The first aim will test the role of the PhoQ/PhoP signal transduction system, as well as additional two-component systems, in enabling adaptation to the expanded niche that leads to blooms during inflammation. The second aim will focus on the role of genes associated with an O-polysaccharide decoration that is detrimental to colonization under standard conditions. This aim will test the hypothesis that this decoration provides protection in the environment of the inflamed intestine. An understanding of the mechanisms that enable adaptation to dysbiotic environments and the role of blooms in imposing selective pressures on the E. coli genome will lead to a better understanding of the dynamic environment of the gastrointestinal tract and to potential strategies for controlling dysbiosis. In addition, many genes required for survival in the context of inflammation may also be important for infection by pathogenic E. coli isolates, either in intestinal or extra-intestinal environments. Thus the selective pressure to bloom during chronic or intermittent inflammation may be critical for the maintenance of genes that contribute to the virulence of pathogenic E. coli. This may lead to new therapies to combat and limit the spread of pathogenic E. coli and related bacteria.