D-serine: trick or treat?

D-serine is an amino acid that has become a focus in recent years due to its unique role in many biological processes. It is a host metabolite in humans with diverse roles in neurotransmission and signalling. Previous work in our group showed that D-serine can play a critical role in controlling expression of pathogenic virulence factors in bacteria, specifically Escherichia coli, as well as impacting microbial community composition through niche specificity. In enterohaemorrhagic E. coli (EHEC), the presence of D-serine results in down regulation of the type 3 secretion system (T3SS), resulting in inability to colonise. In contrast, uropathogenic E. coli (UPEC) can catabolise this metabolite and colonise the bladder where D-serine is present in high concentrations, leading to a urinary tract infections (UTI). Hence, in different pathotypes, D-serine can act as a positive (treat) or negative (trick) environmental stimulus. UPEC and neonatal meningitis E. coli (NMEC) strains often carry the DsdXCA operon which allows for the metabolism of D-serine. This locus is responsible for the detoxification of D-serine, allowing for tolerance of D-serine as a carbon source. My work has focused on understanding the role of D-serine as a signal for gene expression in UPEC and NMEC through the action of the regulator, DsdC. Using global approaches I have characterised the binding sites of DsdC across the chromosome revealing new insights into how this protein contributes to UPEC and NMEC pathogenesis. The work is important as it helps us understand how specific pathogens sense their environment and cause disease.