When and where? Pathogenic differentially sense host D-serine using a universal transporter system to monitor their environment.

Sensing environmental stimuli is critically important for bacteria when faced with the multitude of adversities presented within the host. Responding appropriately to these signals and in turn integrating these responses into the regulatory network of the cell allows bacteria to control precisely when and where they should establish colonization. D-serine is an abundant metabolite of the human urinary tract but is a toxic metabolite for that lack a D-serine tolerance locus. Enterohaemorrhagic (EHEC) cannot catabolize D-serine for this reason and colonize the large intestine specifically, an environment low in D-serine. EHEC can however use D-serine sensing to repress colonization thus signaling the presence of an unfavorable environment. In our recent work (Connolly, et al. PLoS Pathogens (2016) 12(1): e1005359), we describe the discovery of a functional and previously uncharacterized D-serine uptake system in . The genes identified are highly conserved in all lineages but are regulated differentially in unique pathogenic backgrounds. The study identified that EHEC, counter-intuitively, increase D-serine uptake in its presence but that this is a tolerated process and is used to increase the transcriptional response to this signal. It was also found that the system has been integrated into the transcriptional network of EHEC-specific virulence genes, demonstrating an important pathotype-specific adaptation of core genome components.