The life and death of Helicobacter pylori

Abstract

The ability of Helicobacter pylori to survive in the varying acidity of the stomach is considered to be linked to its ability to maintain a tolerable pH in its periplasmic space by acid dependent activation of internal urease activity. Whereas survival of H pylori can occur between a periplasmic pH of 4.0 to 8.0, growth can only occur between a periplasmic pH of 6.0 to 8.0. When urease activity is only able to elevate periplasmic pH to between 4.0 and 6.0, the organisms will survive but not divide. In the absence of division, antibiotics such as clarithromycin and amoxycillin are ineffective. Proton pump inhibitors, by elevating gastric pH, would increase the population of dividing organisms and hence synergise with these antibiotics.

Figures

Figure 1

Comparison of the pH optimum of urease external to H pylori and urease in intact organisms illustrating the 10-fold activation in intact organisms seen between pH 6.5 and 5.5.

Figure 2

Comparison of protein labelling as a function of time using 35S-methionine to label the protein. The four lanes on the right represent proteins synthesised in intact H pylori and the four lanes on the left the medium in which these were suspended. Significant quantities of labelled protein only appear in the medium after about 16 hours of incubation. The protein in the medium shows the same relative labelling pattern as in the whole bacteria. This image is typical of at least three experiments. SOD, superoxide dismutase.

Figure 3

Comparison of the pH range over which H pylori survives to the pH range at which it grows or synthesises protein in the absence of urea. On the figure we indicate the range for which antibiotic sensitivity is expected and illustrate the theoretical effect of proton pump inhibition (PPI) on the population distribution of H pylori between dividing and non-dividing organisms. A, amoxycillin; C, clarithromycin.