Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease.
The gram negative, microaerophilic bacterium Helicobacter pylori colonizes the human gastric mucosa and establishes a chronic infection that is tightly associated with atrophic gastritis, peptic ulcer, and gastric carcinoma. Cloning of the H. pylori cytotoxin gene shows that the protein is synthesized as a 140-kD precursor that is processed to a 94-kD fully active toxin. Oral administration to mice of the purified 94-kD protein caused ulceration and gastric lesions that bear some similarities to the pathology observed in humans. The cloning of the cytotoxin gene and the development of a mouse model of human gastric disease will provide the basis for the understanding of H. pylori pathogenesis and the development of therapeutics and vaccines.
Telford
J L
JL
Department of Molecular Biology, Immunobiological Research Institute Siena, Italy.
Ghiara
P
P
Dell'Orco
M
M
Comanducci
M
M
Burroni
D
D
Bugnoli
M
M
Tecce
M F
MF
Censini
S
S
Covacci
A
A
Xiang
Z
Z
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D003603:Cytotoxins / Q000235:genetics*; D004269:DNA, Bacterial; D004195:Disease Models, Animal; D016481:Helicobacter Infections / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D013272:Stomach Diseases / Q000382:microbiology*; D013276:Stomach Ulcer / Q000382:microbiology
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D004269:DNA, Bacterial; D010446:Peptide Fragments; C074689:VacA protein, Helicobacter pylori