Speaker: Andrew Row, University of Glasgow, UK
Host: Andrea Puhar, Department of Molecular Biology
Venue: Major Groove - find the way here
The gastrointestinal tract presents bacteria with a highly dynamic chemical landscape shaped by host physiology, diet, resident microbiota, and invading pathogens. Within this environment, metabolites act not only as nutrients but also as regulatory signals that influence bacterial gene expression, niche specificity, and evolutionary trajectories. An often-overlooked class of such metabolites are the D-amino acids, which are abundant in the human diet and vary markedly in concentration between host niches. Among these, D-serine is of particular interest, occurring at low micromolar levels in the gut but reaching millimolar concentrations in the urinary tract.
Using Escherichia coli as a model, we examine how D-amino acids function as regulatory cues that shape pathotype-specific behaviour. Uropathogenic E. coli commonly encode the D-serine tolerance locus (dsdCXA), enabling detoxification and utilisation of D-serine and supporting colonization of extraintestinal, nutrient-limited environments. In contrast, intestinal pathotypes such as enterohaemorrhagic E. coli (EHEC) lack this catabolic capacity and are excluded from D-serine-rich niches. Instead, D-serine sensing in EHEC elicits global transcriptional responses, including activation of the SOS response and repression of the type III secretion system required for host attachment, thereby signalling an unfavourable environment.
We further demonstrate that D-serine modulates expression of the pks genomic island encoding the genotoxin colibactin, linking host metabolite availability to regulation of a major virulence and fitness determinant in gut-associated E. coli. Comparative genomic analyses reveal that carriage of dsdCXA is extremely rare alongside key intestinal virulence loci, highlighting an evolutionary incompatibility between D-serine tolerance and niche-specific pathogenic programs. Together, these findings show how D-amino acids act as regulatory “mirror images” that integrate metabolism, virulence, and genome evolution to define niche restriction in E. coli.