ChePep Controls Helicobacter pylori Infection of the Gastric Glands and Chemotaxis in the Epsilonproteobacteria
Open Access
- 1 September 2011
- journal article
- Published by American Society for Microbiology in mBio
- Vol. 2 (4)
- https://doi.org/10.1128/mbio.00098-11
Abstract
Microbes use directed motility to colonize harsh and dynamic environments. We discovered that Helicobacter pylori strains establish bacterial colonies deep in the gastric glands and identified a novel protein, ChePep, necessary to colonize this niche. ChePep is preferentially localized to the flagellar pole. Although mutants lacking ChePep have normal flagellar ultrastructure and are motile, they have a slight defect in swarming ability. By tracking the movement of single bacteria, we found that ∆ChePep mutants cannot control the rotation of their flagella and swim with abnormally frequent reversals. These mutants even sustain bursts of movement backwards with the flagella pulling the bacteria. Genetic analysis of the chemotaxis signaling pathway shows that ChePep regulates flagellar rotation through the chemotaxis system. By examining H. pylori within a microscopic pH gradient, we determined that ChePep is critical for regulating chemotactic behavior. The chePep gene is unique to the Epsilonproteobacteria but is found throughout this diverse group. We expressed ChePep from other members of the Epsilonproteobacteria , including the zoonotic pathogen Campylobacter jejuni and the deep sea hydrothermal vent inhabitant Caminibacter mediatlanticus , in H. pylori and found that ChePep is functionally conserved across this class. ChePep represents a new family of chemotaxis regulators unique to the Epsilonproteobacteria and illustrates the different strategies that microbes have evolved to control motility. IMPORTANCE Helicobacter pylori strains infect half of all humans worldwide and contribute to the development of peptic ulcers and gastric cancer. H. pylori cannot survive within the acidic lumen of the stomach and uses flagella to actively swim to and colonize the protective mucus and epithelium. The chemotaxis system allows H. pylori to navigate by regulating the rotation of its flagella. We identified a new protein, ChePep, which controls chemotaxis in H. pylori . ChePep mutants fail to colonize the gastric glands of mice and are completely outcompeted by normal H. pylori . Genes encoding ChePep are found only in the class Epsilonproteobacteria , which includes the human pathogen Campylobacter jejuni and environmental microbes like the deep-sea hydrothermal vent colonizer Caminibacter mediatlanticus , and we show that ChePep function is conserved in this class. Our study identifies a new colonization factor in H. pylori and also provides insight into the control and evolution of bacterial chemotaxis.Keywords
This publication has 59 references indexed in Scilit:
- CheV: CheW-like coupling proteins at the core of the chemotaxis signaling networkTrends in Microbiology, 2010
- A remote CheZ orthologue retains phosphatase functionMolecular Microbiology, 2010
- A Molecular Mechanism of Bacterial Flagellar Motor SwitchingJournal of Molecular Biology, 2009
- A fixed-time diffusion analysis method determines that the three cheV genes of Helicobacter pylori differentially affect motilityMicrobiology, 2009
- Effect of Helicobacter pylori eradication on gastric carcinogenesisLaboratory Investigation, 2008
- Prospective Identification of a Multilineage Progenitor in Murine Stomach EpitheliumGastroenterology, 2007
- Deep-sea vent ε-proteobacterial genomes provide insights into emergence of pathogensProceedings of the National Academy of Sciences of the United States of America, 2007
- The versatile ε-proteobacteria: key players in sulphidic habitatsNature Reviews Microbiology, 2006
- Making sense of it all: bacterial chemotaxisNature Reviews Molecular Cell Biology, 2004
- Helicobacter pyloriInfection and the Development of Gastric CancerThe New England Journal of Medicine, 2001