How Helicobacter pylori urease may affect external pH and influence growth and motility in the mucus environment: evidence from in-vitro studies.
BACKGROUND
Survival of Helicobacter pylori is dependent upon urease in the cytoplasm and at the bacterial surface. We have sought to clarify how alkaline ammonium salts, released from urea by this enzyme, might alter mucus pH and so affect growth and motility of the bacterium in the gastric mucus environment.


METHODS
Experiments were conducted in vitro to determine how the growth and motility of H. pylori are affected by changes in external pH, and how the bacterium, by hydrolysing urea, alters the pH of the bicarbonate buffer that occurs at the gastric mucosal surface. These data were fitted into experimental models that describe how pH varies within the mucus layer in the acid-secreting stomach.


RESULTS
H. pylori was motile between pH 5 and 8, with optimal motility at pH 5. It grew between pH 6 and 8, with optimal growth at pH 6. The bacterium had urease activity between pH 2.7 and 7.4, as evidenced by pH rises in bicarbonate-buffered solutions of urea. Changes in buffer pH were dependent upon initial pH and urea concentration, with the greatest rate of pH change occurring at pH 3. Modelling experiments utilizing these data indicated that (1) in the absence of urease, H. pylori growth and motility in the mucus layer would be restricted severely by low mucus pH in the acid-secreting stomach, and (2) urease will sometimes inhibit H. pylori growth and motility in the mucus layer by elevating the pH of the mucus environment above pH 8.


CONCLUSIONS
Urease is essential to the growth and motility of H. pylori in the mucus layer in the acid-secreting stomach, but, paradoxically, sometimes it might suppress colonization by raising the mucus pH above 8. This latter effect may protect the bacteria from the adverse consequences of overpopulation.
Sidebotham
Ramon L
RL
Department of Gastroenterology, Imperial College School of Medicine at St Mary's, London, UK.
Worku
Mulugeta L
ML
Karim
Q Najma
QN
Dhir
Nirmal K
NK
Baron
J Hugh
JH
D001639:Bicarbonates / Q000378:metabolism; D015169:Colony Count, Microbial; D003470:Culture Media; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D016480:Helicobacter pylori / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009093:Mucus / Q000378:metabolism / Q000382:microbiology*; D012996:Solutions; D013270:Stomach / Q000382:microbiology*; D014508:Urea / Q000378:metabolism; D014510:Urease / Q000378:metabolism*
D001639:Bicarbonates; D003470:Culture Media; D012996:Solutions; D014508:Urea; D014510:Urease