Research Article: A Highly Conserved Bacterial D-Serine Uptake System Links Host Metabolism and Virulence

Date Published: January 4, 2016

Publisher: Public Library of Science

Author(s): James P. R. Connolly, Mads Gabrielsen, Robert J. Goldstone, Rhys Grinter, Dai Wang, Richard J. Cogdell, Daniel Walker, David G. E. Smith, Andrew J. Roe, Matthew A Mulvey.


The ability of any organism to sense and respond to challenges presented in the environment 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 influence the outcome of infection by repressing the type III secretion system of enterohaemorrhagic Escherichia coli (EHEC) in a concentration-dependent manner. However, exactly how EHEC monitors environmental D-serine is not understood. In this work, we have identified two highly conserved members of the E. coli core genome, encoding an inner membrane 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.

Partial Text

Escherichia coli is an extremely diverse Gram-negative bacterial species, commonly establishing itself as a commensal member of the microbiota early after birth in healthy humans and animals [1]. However, owing to a large degree of genome plasticity, numerous pathogenic forms of E. coli dubbed ‘pathotypes’ have emerged and can be classified broadly according to the site of the body in which they cause infection [2–4]. Pathotypes largely associated with enteric illness include enterohaemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC) and diffusely adherent E. coli (DAEC), which are responsible for varying degrees of diarrheal disease by unique mechanisms. Extraintestinal pathogenic E. coli (ExPEC) colonise and compete in the gastrointestinal tract but have the capacity to disseminate to distal sites. Mostly notably these include urinary tract pathogenic E. coli (UPEC) and the lesser-explored meningitis associated E. coli (MNEC) [4–6].

The ability of a pathogen to sense and respond to stimuli presented in the environment is of critical importance for niche adaptation. Intestinal pathogens must not only be able to identify their preferred site of colonization in terms of nutrient availability but also must compete with the resident microbiota for limited nutrients. Colonization within this complex ecosystem therefore requires effective sensing systems to ensure appropriate gene expression. There has been an emergence in the literature of a wide variety of important signals that EHEC can encounter in the intestinal tract and the complex molecular basis behind how these signals are interpreted allowing colonization of a particular niche within the host gastrointestinal tract is beginning to be unraveled in detail [9].




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