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

PLoS Pathogens

Mads Gabrielsen¹  Rhys Grinter²  Daniel Walker³  James P. R. Connolly³  Andrew J. Roe³  Richard J. Cogdell⁴  David G. E. Smith⁵  Robert J. Goldstone⁵  Dai Wang⁶ 

[1] Cancer Research UK Beatson Institute, Glasgow, United Kingdom;Department of Microbiology, Monash University, Melbourne, Victoria, Australia;Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom;School of Life Sciences, Heriot-Watt University, Edinburgh, United Kingdom;State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, People's Republic of China

关键词: Gene expression;    Regulator genes;    Gene regulation;    Gastrointestinal tract;    Bacterial pathogens;    Bacterial genomics;    Virulence factors;    Transcriptional control;   

DOI  :  10.1371/journal.ppat.1005359

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY