Identification of a High-Affinity Pyruvate Receptor in Escherichia coli

Stefan Behr,Allison R Eberly,Ivica Kristoficova,Philippe Schmitt-Kopplin,Erin J Breland,Maria Hadjifrangiskou,Kirsten Jung,Michael Witting,Corinna Sachs

doi:10.1038/s41598-017-01410-2

Abstract

Two-component systems are crucial for signal perception and modulation of bacterial behavior. Nevertheless, to date, very few ligands have been identified that directly interact with histidine kinases. The histidine kinase/response regulator system YehU/YehT of Escherichia coli is part of a nutrient-sensing network. Here we demonstrate that this system senses the onset of nutrient limitation in amino acid rich media and responds to extracellular pyruvate. Binding of radiolabeled pyruvate was found for full-length YehU in right-side-out membrane vesicles as well as for a truncated, membrane-integrated variant, confirming that YehU is a high-affinity receptor for extracellular pyruvate. Therefore we propose to rename YehU/YehT as BtsS/BtsR, after “Brenztraubensäure”, the name given to pyruvic acid when it was first synthesized. The function of BtsS/BtsR was also assessed in a clinically relevant uropathogenic E. coli strain. Quantitative transcriptional analysis revealed BtsS/BtsR importance during acute and chronic urinary-tract infections.

Highlights

Exponential growth of bacteria in complex, nutrient-rich media usually ends when at least one nutrient has been used up
Numerous studies continue to demonstrate the importance of histidine kinase-mediated signal transduction in bacterial physiology, the natural ligands have been identified for very few histidine kinases[24,25,26]
This study presents compelling evidence demonstrating that the histidine kinase BtsS is a high-affinity receptor for extracellular pyruvate

Summary

Introduction

Exponential growth of bacteria in complex, nutrient-rich media usually ends when at least one nutrient has been used up. The YehU/YehT system is the most widespread representative of its family found in γ-proteobacteria – and many LytS/LytTR-type systems regulate crucial host-specific mechanisms during infection of human or plant hosts by members of this bacterial clade[2]. This system is conserved in non-pathogenic as well as pathogenic E. coli. Our previous studies on YehU/YehT in E. coli identified yjiY as its sole target gene[3] (Fig. 1). We found that the BtsS/BtsR system of uropathogenic E. coli may contribute to acute urinary tract infection

Methods

Results

Conclusion