Background & Aims: The metabolic and urease responses of Helicobacter
pylori to variations in gastric acidity are unknown. The aim of this s
tudy was to determine effects of changes of environmental pH on metabo
lism, urease activity, and survival of H. pylori in an unbuffered envi
ronment. Methods: Bacterial metabolism and urease activity were determ
ined by measuring pH changes in perfused microphysiometer chambers ove
r a pH range from 2.5 to 9.0 with or without urea and survival by rest
oration of metabolism at pH 7.4, Results: Glucose metabolism by acid-a
dapted H. pylori occurred at a perfusion pH between 3.5 and 8.6 and wa
s highest between 7.4 and 8.2. Metabolism was irreversibly inhibited a
t pH <3.5 or >8.6. In the presence of 2.5 mmol/L urea, the chamber pH
increased to about 6.2 during perfusion between pH 5.5 and 4.0. At pH
4.0 and below, urease activity increased several-fold without change o
f chamber pH, Urea in the perfusate enabled retention of metabolism af
ter acid exposure but was toxic at pH 7.4, Conclusions: The metabolic
range of acid-adapted H, pylori is between an environmental pH of 3.5
and 8.6. Extracellular pH-regulated internal urease activity allows me
tabolism in the pH range between 4.0 and 2.5 by maintaining periplasmi
c pH at 6.2. The organism is an acid-tolerant neutralophile due to int
ernal urease activity.