title: ChePep controls Helicobacter pylori Infection of the gastric glands and chemotaxis in the Epsilonproteobacteria.
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 ΔChePep 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, California, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Howitt
authors.forename: Josephine Y
authors.initials: JY
authors.lastname: Lee
authors.forename: Paphavee
authors.initials: P
authors.lastname: Lertsethtakarn
authors.forename: Roger
authors.initials: R
authors.lastname: Vogelmann
authors.forename: Lydia-Marie
authors.initials: LM
authors.lastname: Joubert
authors.forename: Karen M
authors.initials: KM
authors.lastname: Ottemann
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Amieva
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002169:Campylobacter Infections / Q000382:microbiology; D002633:Chemotaxis; D004195:Disease Models, Animal; D020565:Epsilonproteobacteria / Q000737:chemistry / Q000472:pathogenicity* / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D005407:Flagella / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D005753:Gastric Mucosa / Q000382:microbiology*; D017353:Gene Deletion; D016481:Helicobacter Infections / Q000382:microbiology; D008124:Locomotion; D051379:Mice; D008810:Mice, Inbred C57BL; D012376:Rodent Diseases / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors