Chemodetection and Destruction of Host Urea Allows Helicobacter pylori to Locate the Epithelium.
The gastric pathogen Helicobacter pylori interacts intimately with the gastric mucosa to avoid the microbicidal acid in the stomach lumen. The cues H. pylori senses to locate and colonize the gastric epithelium have not been well defined. We show that metabolites emanating from human gastric organoids rapidly attract H. pylori. This response is largely controlled by the bacterial chemoreceptor TlpB, and the main attractant emanating from epithelia is urea. Our previous structural analyses show that TlpB binds urea with high affinity. Here we demonstrate that this tight binding controls highly sensitive responses, allowing detection of urea concentrations as low as 50 nM. Attraction to urea requires that H. pylori urease simultaneously destroys the signal. We propose that H. pylori has evolved a sensitive urea chemodetection and destruction system that allows the bacterium to dynamically and locally modify the host environment to locate the epithelium.
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Julie Y
JY
Huang
Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
Emily Goers
EG
Sweeney
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michael
M
Sigal
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Hai C
HC
Zhang
Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA; Department of Physics, University of Oregon, Eugene, OR 97403, USA.
S James
SJ
Remington
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Michael A
MA
Cantrell
Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Calvin J
CJ
Kuo
Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
Karen
K
Guillemin
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: amieva@stanford.edu.
Manuel R
MR
Amieva
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002633:Chemotaxis; D004195:Disease Models, Animal; D004848:Epithelium / Q000378:metabolism / Q000382:microbiology*; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology*; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D014508:Urea / Q000378:metabolism*; D014510:Urease / Q000378:metabolism*
D001426:Bacterial Proteins; D014508:Urea; D014510:Urease