The global stress response regulator <i>oxyS</i> in an adherent-invasive <i>Escherichia coli</i> strain attenuates experimental colitis

Crohn's disease and ulcerative colitis in humans and experimental immune-mediated colitis in mice are likely due in part to overactive immune responses to resident intestinal bacteria, including certain strains of adherent-invasive <i>Escherichia coli</i> (<i>E. coli</i>) such as <i>E. coli</i> NC101. We have previously shown that specific <i>E. coli</i> NC101 stress responses are upregulated during experimental colitis and attenuate inflammation. However, the roles of broader stress response pathways in <i>E. coli</i> NC101 during experimental colitis are unknown. We hypothesize that the global stress response regulator in <i>E. coli</i>, <i>oxyS</i>, also reduces experimental colitis. We show that intestinal <i>E. coli</i> NC101 upregulate <i>oxyS</i> expression during colitis in monocolonized interleukin-10 deficient mice. Furthermore, we demonstrate that <i>oxyS</i>-sufficient <i>E. coli</i> NC101 have decreased motility and biofilm formation <i>in vitro</i> and attenuated intestinal translocation and colitogenic potential <i>in</i> <i>vivo</i> compared with <i>oxyS-</i>deficient <i>E. coli</i>. These data suggest that activation of a generalized <i>E. coli</i> stress response, <i>oxyS</i>, reduces experimental colitis and may be a potential therapeutic target.