Metalloregulation of Helicobacter pylori physiology and pathogenesis.

Kathryn P Haley,Jennifer A Gaddy

doi:10.3389/fmicb.2015.00911

Abstract

Helicobacter pylori is a Gram-negative spiral-shaped bacterium that colonizes over half of the world's population. Chronic H. pylori infection is associated with increased risk for numerous disease outcomes including gastritis, dysplasia, neoplasia, B-cell lymphoma of mucosal-associated lymphoid tissue (MALT lymphoma), and invasive adenocarcinoma. The complex interactions that occur between pathogen and host are dynamic and exquisitely regulated, and the relationship between H. pylori and its human host are no exception. To successfully colonize, and subsequently persist, within the human stomach H. pylori must temporally regulate numerous genes to ensure localization to the gastric lumen and coordinated expression of virulence factors to subvert the host's innate and adaptive immune response. H. pylori achieves this precise gene regulation by sensing subtle environmental changes including host-mediated alterations in nutrient availability and responding with dramatic global changes in gene expression. Recent studies revealed that the presence or absence of numerous metal ions encountered in the lumen of the stomach, or within host tissues, including nickel, iron, copper and zinc, can influence regulatory networks to alter gene expression in H. pylori. These expression changes modulate the deployment of bacterial virulence factors that can ultimately influence disease outcome. In this review we will discuss the environmental stimuli that are detected by H. pylori as well as the trans regulatory elements, specifically the transcription regulators and transcription factors, that allow for these significant transcriptional shifts.

Highlights

Helicobacter pylori colonizes over half of the world’s population making it arguably the most successful bacterial pathogen (Atherton and Blaser, 2009)
The cytotoxin-associated gene A (CagA) and the vacuolating cytotoxin (VacA) are both implicated in perturbing host cell iron trafficking, and both of these toxins are critical for host persistence (Salama et al, 2000; Tan et al, 2011)
H. pylori utilizes the copAP operon, which encodes a cytoplasmic copper-binding regulator homologous to CopZ from E. coli (CopP) that promotes expression of CopA, a protein which promotes resistance to copper (Beier et al, 1997). These results reveal that tight molecular mechanisms of gene regulation have evolved in the human pathogen H. pylori in response to changes in copper availability, and that these regulatory events are critical for adaptation to the gastric environment

Summary

Metalloregulation of Helicobacter pylori physiology and pathogenesis

Subsequently persist, within the human stomach H. pylori must temporally regulate numerous genes to ensure localization to the gastric lumen and coordinated expression of virulence factors to subvert the host’s innate and adaptive immune response. Recent studies revealed that the presence or absence of numerous metal ions encountered in the lumen of the stomach, or within host tissues, including nickel, iron, copper and zinc, can influence regulatory networks to alter gene expression in H. pylori. These expression changes modulate the deployment of bacterial virulence factors that can influence disease outcome. In this review we will discuss the environmental stimuli that are detected by H. pylori as well as the trans regulatory elements, the transcription regulators and transcription factors, that allow for these significant transcriptional shifts

Introduction

Findings

Conclusions