Adaptation of helicobacter pylori metabolism to persistent gastric colonization

Abstract

Helicobacter pylori is an amazingly successful pathogen that persistently colonizes the hostile gastric niche. Persistence of H. pylori colonization is an important parameter in the clinical outcome of the infection. H. pylori has evolved original mechanisms to colonize and persist within the stomach in spite of the harsh acidic conditions encountered in this environment. Genetic, physiological, and biochemical analyses of H. pylori have revealed peculiar properties of its metabolism, some of which are central in the adaptation to the gastric environment. The abundant enzyme urease is essential for H. pylori resistance to acidity through urea breakdown and production of buffering ammonia. Acid adaptation and management of the potentially toxic amounts of ammonia are closely associated through original transport and metabolic pathways, some of which involve protein complexes. Several metabolic enzymes have been shown to act in addition as genuine virulence factors in particular as immune modulators. This is illustrated by gamma-glutamyl transpeptidase, asparaginase, and arginase. Finally, given the central role of the nickel-dependent enzyme urease, the uptake and intracellular trafficking pathways of this metal essential for H. pylori colonization will be presented. In conclusion, we propose that the constrains of the small H. pylori genome and a very specialized niche has resulted in a close association and in overlapping networks between mechanisms of persistence, acid adaptation and metabolic pathways.