| Popis: |
Urease activity is essential for infection of animal models by Helicobacter pylori. H. pylori urease has a neutral pH optimum between 7.5 and 8.5 but essentially no activity below a pH of 4.5, and activity is lost irreversibly at this pH. The result of pH elevation due to outer urease activity would be that pH would rise to greater than 8.2 in the absence of acid or buffer, and then this neutralophile would not survive. The increase of activity is between 10- and 20-fold when external urease activity is present but can rise much more if surface urease is first washed off or selectively inactivated. Urease activity remains constant down to a pH between 2.5 and 3.0 and is detectable even at a pH of 2.0. This behavior corresponds to that of an acid resistance mechanism, wherein the neutralizing capacity is maintained over a broad range of acidic pH and is lost at pH levels where ammonia generation would generate a toxic environment for the organism. Since what is vital for the organism is the proton motive force (PMF) (pH/potential gradient) across the inner membrane, uncontrolled internal alkalinization would be unsafe, and the objective of creating a safe environment would be achieved by neutralization of the periplasm. The mechanism underlying this pH activation of urease is of vital interest in considering possible selective targets for monotherapy. Direct evidence for acid-activated urea transport was obtained by oocyte expression of one of the genes of the urease gene cluster, UreI. |
