Localization of Helicobacter pylori urease and heat shock protein in human gastric biopsies.
Helicobacter pylori is a spiral, gram-negative bacterium which causes chronic gastritis and plays a critical role in peptic ulcer disease, gastric carcinoma, and gastric lymphoma. H. pylori expresses significant urease activity which is an essential virulence factor. Since a significant fraction of urease activity is located on the surface of the bacterium, the urease molecule is a logical choice as an antigen for a vaccine; currently recombinant urease apoenzyme is being tested as a vaccine in phase II clinical trials. We have recently demonstrated that urease and HspB (a homolog of the GroEL heat shock protein) become associated with the surface of H. pylori in vitro in a novel manner: these cytoplasmic proteins are released by bacterial autolysis and become adsorbed to the surface of intact bacteria, reflecting the unique characteristics of the outer membrane. To determine if similar mechanisms are operative in vivo, we determined the ultrastructural locations of urease and HspB within bacteria present in human gastric biopsies. Our results demonstrate that both urease and HspB are located within the cytoplasm of all bacteria examined in human gastric biopsies. Interestingly, a significant proportion of the bacteria examined also possessed variable amounts of surface-associated urease and HspB antigen (from 5 to 50% of the total antigenic material), indicating that in vivo, H. pylori has surface characteristics which enable it to adsorb cytoplasmic proteins. This is consistent with our altruistic autolysis model in which H. pylori uses genetically programmed bacterial autolysis to release urease and other cytoplasmic proteins which are subsequently adsorbed onto the surface of neighboring viable bacteria. These observations have important implications regarding pathogenesis and development of vaccines for H. pylori.
Dunn
B E
BE
Department of Pathology, Medical College of Wisconsin, Milwaukee, USA.
Vakil
N B
NB
Schneider
B G
BG
Miller
M M
MM
Zitzer
J B
JB
Peutz
T
T
Phadnis
S H
SH
D001426:Bacterial Proteins / Q000032:analysis*; D001706:Biopsy; D005753:Gastric Mucosa / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000032:analysis*; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D016253:Microscopy, Immunoelectron; D013270:Stomach / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D014510:Urease / Q000032:analysis*
D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D014510:Urease