H. Pylori’s Adaptations To Acidity

Despite the fact that H. pylori infection is one of the most common diseases on earth, its exact mode of transmission is not known. Because the organism lives in the  tomach, the assumption is that H. pylori gets to the stomach via the mouth. However, the stomach isn’t a terribly welcoming environment in which to live. It is essentially an acid bath  filled with digestive enzymes, making it hard to imagine how any organism could manage to survive without being digested alive. Indeed, though H. pylori inhabits the  tomach, it has a clear preference for regions of low acidity, which explains the pattern of infection that is observed in diseased tissue. Under normal conditions, the antrum, a less acidic region of the stomach than the stomach body, is often the site of H. pylori colonization in infected people. Evidence of H. pylori’s dislike for acid is also supported by the following observation; when infected patients are given drugs that reduce acid production in the body of the stomach, the distribution of infection shifts toward that area. This suggests that under normal circumstances, the body of the stomach is too acidic for the organism to thrive.

The observation that children, who have less stomach acidity than adults, are more easily infected further suggests that stomach acidity is indeed a barrier to H. pylori growth. H. pylori’s intolerance of acid has led to its occupation of a unique niche in the body. Rather than living in the stomach’s lumen, where acid concentrations are high, H. pylori lives deep in the mucus layer adjacent to the gastric mucosa. The mucus layer—a thick, viscous liquid composed of the glycoprotein mucin—effectively neutralizes the acid in the environment immediately adjacent to the stomach wall. This buffer protects the stomach tissue from its own acid secretions, and is therefore an extremely convenient habitat for a bacterium that cannot tolerate acid.

The difficulty for most organisms seeking to colonize this layer would be the viscosity of the mucin, which most bacteria would be incapable of penetrating; however, H. pylori is equipped with a tuft of between four and seven whip-like structures (called flagella; singular=flagellum) (Figure 3.4) that beat back and forth, propelling it forward and allowing it to swim in liquid environments. This, combined with its corkscrew-like shape, allows H. pylori to burrow deeply into the mucus layer of the stomach, thereby escaping the acidity in the lumen. H. pylori also produces a protein that helps it penetrate the jelly-like layer of mucin. This protein, called collagenase, is believed to partially digest or liquefy the mucin, thereby reducing its viscosity and allowing the organism to move more freely.

H. pylori is very efficient at locating and colonizing its intended target. This is perhaps because the swimming pattern exhibited by H. pylori is not random. H. pylori moves in a directed fashion toward mucin, which means that the organism possesses genes that enable it to somehow “sense” the chemicals of which mucin is composed and follow the chemical trail leading to the mucus layer (a sense that is somewhat akin to smelling). No matter how quickly the bacterium swims, however, it just survive the stomach’s acid at least temporarily to reach the mucin layer. H. pylori is a bacterium that prefers to grow at a neutral pH (that is, neither acidic nor basic). By altering the composition of  its periplasmic space, it essentially forms a bubble around itself so that it can adapt to suit the requirements of its environment. Though the organism is not impenetrable to acid, altering the composition of this space provides a buffer zone between the outside world and its vital insides. In this way, H. pylori protects itself from being burned by the acid while in transit to its destination.

H. pylori accomplishes this feat in part by producing an enzyme called urease. Urease converts urea, a product secreted by the cells of the stomach, into ammonia and carbon dioxide. Ammonia is a weakly basic substance that neutralizes the acidity  of the stomach in the immediate vicinity of the H. pylori organism. Because this reaction occurs in the organism’s periplasmic space, H. pylori effectively bathes itself in an acidbuffering solution. As long as the bacterium is surrounded by this halo of ammonia as it moves through the stomach, it is relatively impervious to the stomach’s acid. H. pylori produces another enzyme, alpha-carbonic anhydrase (?-CA), that also contributes to this de acidification process. ?-CA cooperates with urease in the process of deacidification by converting the carbon dioxide produced by urease into bicarbonate (a compound similar to baking soda).

Bicarbonate is another weakly basic chemical that neutralizes the stomach’s acidity. The importance of these enzymes has been demonstrated by studies performed with experimental strains of H. pylori that lack either urease or ?-CA. Urease-negative strains are particularly inefficient at colonizing the stomach and have been unable to produce ulcers in experimental animals. In other experiments in which compounds that inhibit the urease enzyme were administered, the effect was the same: the bacterium was unable to colonize the stomachs of animals. Similarly, studies conducted with strains lacking ?-CA demonstrated that mutants were much less acid-tolerant than the strains containing.