Voice of Science and Fairness

My personal opinion on science, religion and politics

Amazing adaptation: How does a gastric pathogen survive in the acidic mammalian stomach?

(So beautiful are the molecular mechanisms for acid resistance in the gastric pathogen that I felt guilty to have aimed to reduce the beauty to physics and chemistry.)

Helicobacter pylori is acid-resistant but not acidophilic. Its cellular machinery works better at neutral pH than at acidic pH.

Mammalian stomach is highly acidic. Without an efficient acid-resistant mechanism, the cytoplasm of H. pylori would acidify, the cellular machinery in the cytoplasm will fail to work, and the H. pylori will die.

H. pylori cell needs not only an efficient acid-resistant mechanism, but also a mechanism that can be passed to its daughter cells.

Any mechanism that responds to environmental changes, e.g., from neutral pH to acidic pH, requires, at the minimum, a sensor of the change and an effector that responds to the change. When we feel hot, we take off clothes. When a sexually mature male fish senses the presence of a sexually mature female, it gets excited. When H. pylori senses a change in pH, it unfolds a large number of changes to maintain its pH homeostasis.

The acid-resistance mechanism involves multiple sensors and effectors embedded in several two-component systems which integrates a large number of proteins and their functions centered on the regulated function of a urease gene cluster. Firstly, urease expression above a base level needs to be finely tuned at different ambient pH. Secondly, as nickel is needed to activate urease, nickel homeostasis needs to be maintained by proteins that import and export nickel ions, and sequester, store and release nickel when needed. Thirdly, urease accessary proteins that activate urease activity by nickel insertion need to be expressed. Finally, a reliable source of urea needs to be maintained by both intrinsic and extrinsic sources of urea. Remarkably, all these complicated processes can be reduced to simple physics and chemistry in this review from a unique perspective.

Please read the paper.

Xia, X. Multiple regulatory mechanisms for pH homeostasis in the gastric pathogen, Helicobacter pylori. in Advances in Genetics (Academic Press, 2022).