Factors affecting growth and antibiotic susceptibility of Helicobacter pylori: effect of pH and urea on the survival of a wild-type strain and a urease-deficient mutant.
This study investigated how pH and the presence of urea affect the survival and growth of Helicobacter pylori and whether these factors affect susceptibility to antibiotics in vitro. The viability of a wild-type strain and a urease-deficient mutant of H. pylori was studied after incubation for 1 h in buffers at different pH values at 37 degrees C under microaerophilic conditions. Viable counts were not affected at pH 5 and pH 7. In buffer at pH 3, there were no viable organisms, but urea (6.25 mM) protected the wild-type strain, which survived well. At pH 9, urea further reduced the viability of H. pylori and flurofamide almost abolished the effect of urea on the wild-type strain. Neither urea nor flurofamide affected the viability of the urease-deficient mutant under the same conditions. Growth was also pH dependent and was enhanced in shake-cultures. At pH 5, urea supported growth of the wild-type strain, but at pH 7 a toxic effect on the bacteria was observed. Growth of H. pylori at pH 5.9 was poor, and susceptibility to amoxycillin, erythromycin and clarithromycin was markedly less than at pH 7.2 and 7.9. The bactericidal activities of metronidazole and tetracycline were similar at the different pH values studied. At neutral pH the killing rates of amoxycillin and clarithromycin were growth rate dependent. Susceptibility to metronidazole was enhanced in stationary cultures. The interaction obtained between the proton pump inhibitor, omeprazole, and amoxycillin at pH 7 was of additive type. These results suggest that pH and growth conditions may be important in the antibacterial efficacy of different antibiotics in vivo and also provide a possible explanation for the potentiating effect of omeprazole with antibiotics in the treatment of H. pylori infections.
Sjöström
J E
JE
Department of Cell Biology, Astra Hässle AB, Mölndal, Sweden.
Larsson
H
H
D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D004347:Drug Interactions; D004381:Duodenal Ulcer / Q000382:microbiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016480:Helicobacter pylori / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009853:Omeprazole / Q000494:pharmacology; D010406:Penicillins / Q000494:pharmacology; D014508:Urea / Q000378:metabolism / Q000494:pharmacology*; D014510:Urease / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D010406:Penicillins; D008795:Metronidazole; C032764:flurofamide; D000658:Amoxicillin; D014508:Urea; D014510:Urease; D017291:Clarithromycin; D009853:Omeprazole