RESEARCH ARTICLE A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and

The ability of any organism to sense and respond to challenges presented in the environ-ment is critically important for promoting or restricting colonization of specific sites. Recent work has demonstrated that the host metabolite D-serine has the ability to markedly influ-ence the outcome of infection by repressing the type III secretion system of enterohaemor-rhagic Escherichia coli (EHEC) in a concentration-dependent manner. However, exactly how EHECmonitors environmental D-serine is not understood. In this work, we have identi-fied two highly conserved members of the E. coli core genome, encoding an inner mem-brane transporter and a transcriptional regulator, which collectively help to “sense ” levels of D-serine by regulating its uptake from the environment and in turn influencing global gene expression. Both proteins are required for full expression of the type III secretion system and diversely regulated prophage-encoded effector proteins demonstrating an important infection-relevant adaptation of the core genome. We propose that this system acts as a key safety net, sampling the environment for this metabolite, thereby promoting colonization of EHEC to favorable sites within the host