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Presented by Mihaela C. Badea-Mic

Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: A strategy for bacterial survival. Alain P. Gobert, David J. McGee, Mahmood Akhtar, George L. Mendz, Jamie C. Newton, Yulan Cheng, Harry L. T. Mobley, and Keith T. Wilson. Presented by Mihaela C. Badea-Mic.

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Presented by Mihaela C. Badea-Mic

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  1. Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: A strategy for bacterial survival Alain P. Gobert, David J. McGee, Mahmood Akhtar, George L. Mendz, Jamie C. Newton, Yulan Cheng, HarryL. T. Mobley,and Keith T. Wilson Presented by Mihaela C. Badea-Mic

  2. So, Who Am I? • Gram negative bacteria inside the stomach and duodenum The Helicobacter Foundation

  3. 1983-Campylobacterpyloridis 1997- Tomb et al sequenced the HP genome The Helicobacter Foundation, 2005 Who discovered me?

  4. Prevalence (USA) African-American Hispanic Eastern Europeans UBIQUITOUS 50% world population The Helicobacter Foundation, 2005 Epidemiology

  5. The most common route of H. Pylori infection Oral to oral Fecal to oral PS: watch your pets! Pathophysiology

  6. Histology The Helicobacter Foundation, 2005

  7. ・ Breath test - Based on the detection of the products of urea Diagnosis The Helicobacter Foundation, 2005

  8. Diagnosis- cont. ・ Esophagogastroduodenoscopy with biopsy ・ H. Pylori fecal antigen ・ H. Pylori serology

  9. Diseases The Helicobacter Foundation, 2005

  10. Diseases- cont. • Gastric and duodenal ulcers • Gastric cancer ( 90%) • Non-ulcer dyspepsia • Weird syndromes

  11. Treatment • Antidiarrheals – bistmuth • Antibiotics - metronidazole, tetracycline, amoxicilin • Proton pump inhibitors - omeprazole, lansoprazole • H2 receptor blockers – ranitidine, famotidine

  12. My survival strategies D. S. Merrel et al, 2004

  13. My virulence factors D. M. Monack et al, 2004

  14. Details D. M. Monack et al, 2004

  15. And now…finally the paper • Activated macrophages produce NO using L-arginine as a substrate • H. Pylori arginase competes with NOS2 for the substrate • H. Pylori converts the substrate to urea and L-ornithine, not NO • rocF gene encodes arginase • Mutations in rocF gene helps the NO to kill H. Pylori

  16. Experiment # 1A • Hypothesis - the activated macrophage production ofNO is inhibited by wt H. Pylori atphysiologic L-arginine concentrations

  17. Experiment #1A – cont. Conclusion: -only the wt H. Pylori inhibited NO released - the arginase deficient H. Pylori did not inhibit

  18. Experiment # 1B • Conclusion: adding more substrate will stop the competitive inhibition between H. pylori and activated macrophages

  19. Experiment # 2 • Hypothesis – H. Pylori wt compete for the same substrate with activated macrophages. This substrate is L-arginine .

  20. Experiment # 2 –cont. • Conclusion • the wt H. Pylori uses L-arginine decreasing the macrophage NO production because of the loss of the substrate • the rocF mutant does not use the L-arginine

  21. Hypothesis – the macrophage production of NO is regulated by the H. Pylori arginase independently of iNOS expression Conclusion- both H. Pylori induce iNOS mRNA expression Experiment # 3

  22. Experiment # 4 • Hypothesis – The bacterial arginase inhibits the release of NO by preformed iNOS in macrophages.

  23. Conclusion: the wt H. Pylori inhibits macrophage NO production by the preactivated cells Experiment # 4-cont

  24. Hypothesis – Only viable H.pylori can inhibit the release of macrophage NO Conclusion : only live H. Pylori can consume the substrate in order to inhibit theiNOS Experiment # 5

  25. Hypothesis – Inhibition of the host cell NO production is a survival strategy for H. Pylori . Conclusion – the wt H. Pylori has an increased rate of survival in comparison with rocF mutant H. Pylori in the presence of macrophages . Experiment # 6

  26. Experiment # 6 A

  27. Experiment # 6B Conclusion: The rocF mutant H. Pylori survives in the presence of iNOS -/- macrophages.

  28. Summary • Bacterial arginase evolutionary adaptation survival strategy for H. pylori gastric mucosa protection

  29. Don’t let your kids kiss us! The Helicobacter Foundation, 2005

  30. Invitation

  31. That is all I had to say… • The End!

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