Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates.

Abstract

Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 260-320 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections.

• Authors: Jed W Fahey, Katherine K Stephenson, Kristina L Wade, Paul Talalay
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 435 Issue 1 Pg. 1-7 (May 24 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23583386 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Isothiocyanates
• Sulfoxides
• Thiocyanates
• Urease
• sulforaphane

Topics

• Anti-Bacterial Agents (chemistry, pharmacology)
• Bacterial Proteins (antagonists & inhibitors, metabolism)
• Brassica (chemistry)
• Dose-Response Relationship, Drug
• Helicobacter Infections (microbiology, prevention & control)
• Helicobacter pylori (drug effects, enzymology)
• Humans
• Isothiocyanates (chemistry, pharmacology)
• Kinetics
• Microbial Sensitivity Tests
• Molecular Structure
• Spectrophotometry, Ultraviolet
• Sulfoxides
• Thiocyanates (chemistry, pharmacology)
• Time Factors
• Urease (antagonists & inhibitors, metabolism)