Paf-acether synthesis by Helicobacter pylori
Y Denizot1, I Sobhani, J C Rambaud
1INSERM U200, Clamart, France.
Abstract:
Clinical studies suggest that Helicobacter pylori may play a role in the pathogenesis of gastroduodenal ulcers in man but direct evidence of mucosal injury by this microorganism is still lacking. Paf-acether (paf) causes a number of disorders including ischaemic bowel necrosis and gastroduodenal ulceration. Since paf is produced by Escherichia coli, we investigated whether it could be synthesised by H pylori. Five H pylori isolates were collected from antral biopsy specimens from patients with gastritis and duodenal ulcer and cultured with selective antibiotics. Colonies obtained from both blood agar and brucella broth medium were used. Paf was determined by platelet aggregation assay after ethanolic extraction and subsequent purification by high performance liquid chromatography. Paf was detected in H pylori in blood agar plates (680 (390) pg paf/1 x 10(6) organisms) but not in bacteria cultured on brucella broth medium. Supplementation of the latter medium with lyso paf and acetyl-CoA, two paf precursors present in high amounts in the mammalian intestine, induced paf production in three of five isolates. The platelet aggregating material extracted from H pylori exhibited biological and physiochemical characteristics identical to those of paf released from eukaryotic cells. These findings suggest that H pylori may add to the local production of paf in inflamed gastric mucosa.
Insights
Helicobacter pylori produces platelet-activating factor (paf), a substance linked to gastroduodenal ulcers. This finding suggests H. pylori may contribute to ulcer development in the stomach lining.
Area of Science:
- Microbiology
- Gastroenterology
- Biochemistry
Background:
- Clinical studies implicate Helicobacter pylori in gastroduodenal ulcer pathogenesis.
- Platelet-activating factor (paf) is known to cause gastrointestinal disorders, including ulceration.
Purpose of the Study:
- To investigate the potential synthesis of paf by H. pylori.
- To determine if H. pylori contributes to local paf production in the gastric mucosa.
Main Methods:
- H. pylori isolates from patients with gastritis and duodenal ulcers were cultured.
- Paf production was assessed using platelet aggregation assays after ethanolic extraction and HPLC purification.
- Bacteria were cultured on blood agar and brucella broth medium, with and without paf precursors.
Main Results:
- Paf was detected in H. pylori cultured on blood agar, but not on brucella broth medium.
- Supplementation with paf precursors (lyso paf and acetyl-CoA) induced paf production in some isolates.
- Extracted platelet aggregating material showed characteristics identical to eukaryotic paf.
Conclusions:
- H. pylori can synthesize paf under specific conditions.
- H. pylori may contribute to the local production of paf in inflamed gastric mucosa, potentially playing a role in ulcer pathogenesis.
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