Genetic Determinant Governs H Pylori Behavior

Researchers have found that the ulcer-causing bacteria Helicobacter pylori requires a specific gene to be able to follow the pH gradient from the acidic reaches of the stomach to the more alkaline region of the gastric mucosa. Mutants lacking this gene were unable to infect a line of susceptible mice.

Investigators at the University of Virginia (Charlottesville, USA) used a microscope slide-based pH gradient assay and video data collection system to document pH-tactic behavior. In response to hydrochloric acid, H pylori changed its swimming pattern from straight-line random swimming to arcing or circular patterns that moved the motile population away from the strong acid. Bacteria in more-alkaline regions did not swim toward the acid.

To identify the chemoreceptors responsible for the transduction of pH-tactic signals, genetic engineering was used to construct mutations in each of the four known chemoreceptor genes (tlpA, tlpB, tlpC, and tlpD) in H pylori strain SS1 and a motile variant of strain KE26695. Results of studies with these mutant strains published in the April 2006 edition of the Journal of Bacteriology revealed that only tlpB mutants were defective for pH taxis.

While tlpA, tlpC, and tlpD mutants were able to colonize mice to near wild-type levels, tlpB mutants failed to infect a line of highly permissive C57BL/6 mice. Replacement of tlpB restored both pH taxis and infectivity for mice.

"Because pH sensing ability is essential for colonization and persistence in the stomach lining tissue, the tlpB pH receptor might represent a novel target for the development of treatments that can interfere with this behavior,” said senior author Dr. Paul S. Hoffman, professor of infectious diseases at the University of Virginia. "H pylori infections occur most often in developing countries that cannot afford the cost of miracle drugs. Perhaps a narrow-spectrum drug designed to block the chemoreceptor would be less expensive to develop.”



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