Ulcer-causing pathogen uses hydrogen for energy

December 02, 2002

In a groundbreaking study, a North Carolina State University microbiologist has discovered that the bacteria associated with almost all human ulcers - one that is also correlated with the development of certain types of gastric cancer in humans - uses hydrogen as an energy source.

The finding is novel because most bacteria use sugars and other carbohydrates to grow, says Dr. Jonathan Olson, assistant professor of microbiology at NC State. The human pathogen Helicobacter pylori does not.

"No one has ever suspected hydrogen to be an energy source for pathogens," Olson said. "Now we have a whole new target for antibiotics for this particular bacteria."

The research is described in a paper published in the Friday, Nov. 29 edition of Science.

The study was performed at the University of Georgia, where Olson was a member of the research faculty before joining the microbiology faculty at NC State this summer. Dr. Robert J. Maier, a microbiologist at the University of Georgia, is a co-author of the paper. The work was supported by the Georgia Research Alliance.

H. pylori is only found in humans, Olson says. The bacteria infects greater than 50 percent of the world's population, and persists until it is treated. If left untreated, the bacteria can give rise to ulcers and two different kinds of cancer.

H. pylori contains an enzyme - hydrogenase - that uses hydrogen as an energy source. "If we were to develop a drug to inhibit the hydrogenase enzyme, we could eradicate ulcers in humans," Olson says.

Using mice as a model, the scientists discovered that mice stomachs contained more than enough hydrogen to support the growth of H. pylori. The study showed that mice stomachs contained 10 to 50 times more hydrogen than the bacteria needs to grow.

Moreover, when the scientists created a mutant strain of H. pylori without hydrogenase, only 24 percent of these mutants colonized in mice, as opposed to 100 percent of the parent strain that was able to utilize hydrogen, Olson says. The mutants that did colonize in mice also had lower levels of bacteria, he says.

Hydrogenase is a complicated enzyme that is not made by humans. Olson says that finding an antibiotic that is specifically targeted to inhibit the enzyme shouldn't be toxic to other human enzymes. However, no compounds that specifically inhibit hydrogenase currently exist, so the development of such a drug will come later rather than sooner, Olson says.

Because not many bacteria use hydrogen to grow, Olson and Maier are among a small fraternity of scientists who study bacterial hydrogen utilization. Most of these bacteria exist in hydrogen-rich environments, Olson says, mainly in agricultural areas.

Olson's lab at NC State is presently studying a hydrogen-utilizing bacteria that is the most common cause of food poisoning.
-end-
Note to editors: An abstract of the Science paper follows.

"Molecular Hydrogen as an Energy Source for Helicobacter pylori"
Authors: Jonathan W. Olson, North Carolina State University; Robert J. Maier, University of Georgia
Published: Nov. 29, 2002, in Science
Abstract: The gastric pathogen Helicobacter pylori is known to be able to use molecular hydrogen as a respiratory substrate when grown in the laboratory. We found that hydrogen is available in the gastric mucosa of mice and that its use greatly increased the stomach colonization by H. pylori. Hydrogenase activity in H. pylori is constitutive but increased fivefold upon incubation with hydrogen. Hydrogen concentrations measured in the stomachs of live mice were found to be 10 to 50 times as high as the H. pylori affinity for hydrogen. A hydrogenase mutant strain is much less efficient in its colonization of mice. Therefore, hydrogen present in animals as a consequence of normal colonic flora is an energy-yielding substrate that can facilitate the maintenance of a pathogenic bacterium.

Additional Media Contact:
Mick Kulikowski, News Services, 919-515-3470.

North Carolina State University

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