Eradication of Helicobacter pylori

H. pylori is a Gram-negative neutralophile (e.g., grows best at pH 7.0 and does not grow below pH 5.0) that is unique in having acclimated to the gastric environment to the extent that it is able to infect and colonize the human stomach.32 Other pathogenic neutralophiles can survive in gastric acidity by acid-tolerant or -resistant mechanisms, but they cannot colonize the stomach.33 Acid acclimation by H. pylori depends on the expression of several genes, in particular, the genes of the urease cluster.34 These consist of a promoter, the structural subunit genes, ureA and ureB, followed by a second promoter and then urel, ureE, ureF, ureG, and ureH. The last four genes are required for Ni2 + insertion into the UreA/UreB apoenzyme complex, to form active urease. UreI is a proton-gated urea channel that allows urea entry to the intrabacterial urease, enhancing the production of NH3 and CO2 up to 40-fold.35 The NH3 is able to neutralize entering acid in both the periplasm and cytoplasm of the organism, and CO2 is converted to the buffer HCO^ in both the cytoplasm and periplasm.36 H. pylori is unique in being able to control the pH of its periplasm to ~6.1, the effective pKa of the HCO3^/CO2 couple, at a medium pH as low as ~2.5 in the presence of urea. This property allows growth in specific regions of the stomach. Gastric juice contains 1-3 mM urea, and this is sufficient for colonization by the organism. Consistent with the important role of the urease system, deletion mutants of UreI or the carbonic anhydrases or urease negative mutants are not able to colonize animal models such as the mouse or the gerbil.37,38 The urease/carbonic anhydrase mechanism for acid acclimation is shown in Figure 6.

The ability to acclimate to gastric acidity implies that H. pylori seeks a favorable milieu in which to multiply, but in other locations may just resist acid and not divide. Hence, the population of H. pylori in the human stomach consists of bacteria in both stationary and log phases.

H. pylori infection always results in gastritis, and can progress to gastric or duodenal ulceration, and increase the risk of gastric cancer up to 20-fold.3 Although some believe that the organism is a harmless or even a beneficial commensal,39 the vast majority of clinical data dispute this opinion. Eradication of H. pylori, if present, is the appropriate therapeutic choice.

Treatment with antibiotics (e.g., amoxicillin, clarithromycin, or metronidazole alone or in combination) cannot eradicate the organism, presumably because many of the bacteria are in the stationary phase and thus not affected by such growth-dependent antibiotics. An essential adjunct of therapy is the reduction of acid secretion by any PPI or

Was this article helpful?

0 0
Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook

Post a comment