Gastric antibacterial efficiency is different for pepsin A and C

Abstract

The gastric lumen represents a bactericidal barrier, whose major components are an acidic pH and a family of isoenzymes of the gastric aspartate protease, pepsin. To evaluate whether specific pepsins are specialized in antibacterial protection, we tested their effects on the gastric pathogen Helicobacter pylori. In a recent study we found pepsin to affect the motility of the bacteria, one of its most important virulence factors. We were able to show that the antibacterial effect of pepsin occurs in two phases: rapid loss of motility and subsequent destruction. In the present study we used the rapid pepsin-induced bacterial immobilization as a marker of antibacterial efficiency. The proteolytic activity of different pepsins was normalized to values between 2 and 200 U/ml in the hemoglobin degradation test of Anson, performed at pH 2 and 5. We found that pepsin C completely inactivates H. pylori at proteolytic activities of 2 (pH 5) and 20 (pH 2) U/ml. In contrast, the activities of pepsin A and chymosin required to affect Helicobacter motility were ten times higher.

The spatial orientation of Helicobacter pylori in the gastric mucus

“…To demonstrate that the combined reduction of arterial pH and bicarbonate secretion does indeed lead to the predicted elimination of the mucus pH, we conducted an additional series of experiments in the explanted antrum mucosa of the guinea pig, a model system that permits direct pH measurements with ultrafine-tipped double barrel microelectrodes (2,3). The conditions of low plasma pH and bicarbonate concentration used in the gerbil and mouse experiments were reproduced in this system, and the pH values in the gastric mucus were measured.…”

“…The technique of removing nanoliter samples of mucus has been described (3,10). The sampling device operates by heating up or cooling down a sealed pipette filled with silicon oil.…”

“…The mucus is continuously secreted in the glands and by surface epithelial cells and is degraded at the luminal surface (2). Because of this rapid mucus turnover, the bacteria need motility and spatial orientation to avoid being carried into the lumen, where the acidic pH inhibits growth and paralyzes motility (3,4). Orientation therefore plays a central role in acute colonization and the chronic persistence of H. pylori.…”

“…We have previously developed a method to precisely determine the distribution and colonization density of Helicobacter felis in the gastric mucus of mice in vivo (3). This method uses a micromanipulator-controlled sampling device (10) to extract nanoliter samples from the mucus and mucosa of anesthetized animals.…”

Specific Therapeutic Schemes of Omeprazole Affect the Orientation of Helicobacter pylori

“…Helicobacter pylori bacteria which lose their guiding gradient in the gastric mucus spread over the entire mucus layer and into the lumen (19). Depending on the actual pH, the remaining activity of pepsin C in the lumen causes a loss of H. pylori motility (17,18), the bacteria are irretrievably lost, and the bacterial load is reduced. In contrast, two subsequent PPI administrations in shorter time intervals, in which the gastric pH remained neutralized, had no effect on H. pylori orientation.…”