To identify
Escherichia coli proteins involved in adaptation to intestinal
inflammation, mice were monoassociated with the colitogenic E. coli strain UNC or with the probiotic E. coli strain Nissle. Intestinal
inflammation was induced by treating the mice with 3.5%
dextran sodium sulfate (DSS). Differentially expressed
proteins in E. coli strains collected from cecal contents were identified by 2-dimensional difference gel electrophoresis. In both strains, acute
inflammation led to the downregulation of pathways involved in
carbohydrate breakdown and energy generation. Accordingly, DSS-treated mice had lower concentrations of bacterial fermentation products in their cecal contents than control mice. Differentially expressed
proteins also included the Fe-S cluster repair
protein NfuA, the
tryptophanase TnaA, and the uncharacterized
protein YggE. NfuA expression was 3-fold higher in E. coli strains from DSS-treated than from control mice. Reporter experiments confirmed the induction of nfuA in response to
iron deprivation, mimicking Fe-S cluster destruction by
inflammation. YggE expression, which has been reported to reduce the intracellular level of
reactive oxygen species, was 4- to 8-fold higher in E. coli Nissle than in E. coli UNC. This was confirmed by in vitro reporter gene assays indicating that Nissle is better equipped to cope with oxidative stress than UNC. Nissle isolated from DSS-treated and control mice had TnaA levels 4- to 7-fold-higher than those of UNC. Levels of
indole resulting from the TnaA reaction were higher in control animals associated with E. coli Nissle. Because of its anti-inflammatory effect,
indole is hypothesized to be involved in the extension of the remission phase in
ulcerative colitis described for E. coli Nissle.