Ureases as a target for the treatment of gastric and urinary infections.
Urease is known to be a major contributor to pathologies induced by Helicobacter pylori and Proteus species. In H pylori, urease allows the bacteria to survive in an acidic gastric environment during colonisation, playing an important role in the pathogenesis of gastric and peptic ulcers. Ureolytic activity also results in the production of ammonia in close proximity to the gastric epithelium, causing cell damage and inflammation. In the case of Proteus species (notably Proteus mirabilis) infection, stones are formed due to the presence of ammonia and carbon dioxide released by urease action. In addition, the ammonia released is able to damage the glycosaminoglycan layer, which protects the urothelial surface against bacterial infection. In this context, the administration of urease inhibitors may be an effective therapy for urease-dependent pathogenic bacteria. This is a review of the role of ureases in H pylori and Proteus species infections, focussing on the biochemical and clinical aspects of the most promising and/or potent urease inhibitors for the treatment of gastric and urinary tract infections.
Follmer
C
C
Department of Physical Chemistry, Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro 21941-909, Brazil. follmer@iq.ufrj.br
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005756:Gastritis / Q000188:drug therapy* / Q000382:microbiology; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000201:enzymology / Q000472:pathogenicity; D006801:Humans; D011511:Proteus / Q000201:enzymology / Q000472:pathogenicity; D011512:Proteus Infections / Q000188:drug therapy*; D014510:Urease / Q000037:antagonists & inhibitors* / Q000502:physiology; D014552:Urinary Tract Infections / Q000188:drug therapy*; D014774:Virulence
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D014510:Urease