presented by mihaela c. badea-mic
DESCRIPTION
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. - PowerPoint PPT PresentationTRANSCRIPT
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Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: A strategy for bacterial survivalAlain 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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So, Who Am I?
• Gram negative bacteria inside the stomach and duodenum
The Helicobacter Foundation
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Who discovered me?
• 1983-Campylobacter pyloridis
• 1997- Tomb et al sequenced the HP genome
• The Helicobacter Foundation, 2005
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Epidemiology• Prevalence (USA)• African-American• Hispanic• Eastern Europeans
• UBIQUITOUS• 50% world population
• The Helicobacter Foundation, 2005
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Pathophysiology
• The most common route of H. Pylori infection• Oral to oral• Fecal to oral
PS: watch your pets!
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Histology
The Helicobacter Foundation, 2005
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Diagnosis
・ Breath test
- Based on the detection of the products of urea
The Helicobacter Foundation, 2005
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Diagnosis- cont.
・ Esophagogastroduodenoscopy with biopsy
・ H. Pylori fecal antigen・ H. Pylori serology
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Diseases
The Helicobacter Foundation, 2005
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Diseases- cont.
• Gastric and duodenal ulcers• Gastric cancer ( 90%)• Non-ulcer dyspepsia• Weird syndromes
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Treatment
• Antidiarrheals – bistmuth• Antibiotics - metronidazole, tetracycline,
amoxicilin• Proton pump inhibitors - omeprazole,
lansoprazole• H2 receptor blockers – ranitidine,
famotidine
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My survival strategies
D. S. Merrel et al, 2004
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My virulence factors
D. M. Monack et al, 2004
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Details
D. M. Monack et al, 2004
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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
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Experiment # 1A
• Hypothesis - the activated macrophage production of NO is inhibited by wt H. Pylori at physiologic L-arginine concentrations
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Experiment #1A – cont.
Conclusion:
-only the wt H. Pylori inhibited NO released
- the arginase deficient H. Pylori did not inhibit
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Experiment # 1B
• Conclusion: adding more substrate
will stop the competitive inhibition between H. pylori and activated macrophages
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Experiment # 2
• Hypothesis – H. Pylori wt compete for the same substrate with activated macrophages. This substrate is L-arginine .
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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
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Experiment # 3
• 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
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Experiment # 4
• Hypothesis – The bacterial arginase inhibits the release of NO by preformed iNOS in macrophages.
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Experiment # 4-cont
• Conclusion:the wt H. Pylori inhibits
macrophage NO production by the preactivated cells
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Experiment # 5
• 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 the iNOS
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Experiment # 6
• 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 .
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Experiment # 6 A
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Experiment # 6B
Conclusion:The rocF mutant H. Pylori survives in the presence of iNOS -/- macrophages.
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Summary
• Bacterial arginase evolutionary adaptation survival strategy for H. pylori gastric mucosa protection
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Don’t let your kids kiss us!
The Helicobacter Foundation, 2005
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Invitation
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That is all I had to say…
• The End!