Saturday, December 5, 2009

How Helicobacter Gets Around
Helicobacter pylori is the only bacterium (that I know of) that is capable of colonizing the rather intimidating environment of the human stomach. A very low pH, and a thick viscous and elastic mucus, make for a difficult niche to inhabit. But for a bacterium, the payoffHelicobacter must move trhough thick mucus to gain protection in the gastric pitss are huge: a constant supply for nutrients, no other prokaryotic competition, and little interaction with the immune system.
It is well described that to survive the low pH, Helicobacter utilizes a urease system. Taking in urea present in the stomach, the bacterium creates and secretes ammonia, raising the pH to nearly neutral. It is also known that to escape the lower pH of the stomach lumen, and to successfully colonize, Helicobacter must move through the thick gastric mucus lining the stomach into gastric pits within the stomach epithelium. The question that this phenomenon raises is how the bacterium is able to be motile through the very thick, viscous, and elastic mucus.

Some ways Helicobacter could solve this problem include: very strong flagellar power using brute force to tunnel through the mucus, or via secretion of mucus degrading enzymes to breakdown the mucus making it more liquid. It is known that as the pH of gastric mucus is raised, the gel-like structure becomes less organized and more liquid. Relatively recently, a study in the Proceedings of the National Academy of Sciences, has directly connected the raise in pH due to Helicobacter urease, to motility and liquidity.

Using techniques in rheology that are well beyond my expertise, the authors show that in the presence of both urea and Helicobacter, low pH mucus becomes both less viscous and elastic, and moreA random bacterial walk toward a chemoattractant liquid as the pH raises. However, without urea, Helicobacter is unable to transform the mucus from a gel-like structure.

Next, using live cell imaging techniques, the authors demonstrated that Helicobacter cannot be motile in raised pH mucus gel, without urea, but can be highly motile in mucus solution at the same pH. These two findings indicated that motility was a direct function of the structure of the surrounding mucus, which was a direct function of the pH. Finally, using a dye that fluoresces at more neutral pH, the authors were able to show that at the exact point that the pH is raised by Helicobacter, the mucus becomes more liquid, and the cells become motile.

These findings show that Helicobacter uses the same urease system to both change the pH to a more hospitable level, while at the same time alter the structure of mucus to allow motility to the more protected gastric pits for colonization.

Celli, J., Turner, B., Afdhal, N., Keates, S., Ghiran, I., Kelly, C., Ewoldt, R., McKinley, G., So, P., Erramilli, S., & Bansil, R. (2009). Helicobacter pylori moves through mucus by reducing mucin viscoelasticity Proceedings of the National Academy of Sciences, 106 (34), 14321-14326 DOI: 10.1073/pnas.0903438106

1 comment:

Lab Rat said...

Weakening the protective mucus layer inside the stomach probably helps in ulcer formation as well.