St. Louis, April 13 -- Scientists in Halifax, Nova Scotia, and St. Louis, Mo., have discovered why the bacterium Helicobacter pylori, which causes peptic ulcer disease, is sensitive to metronidazole, a critical component of the leading H. pylori therapy. They also have determined how the bacterium becomes resistant to this drug. H. pylori infects more than half the world's people and is a major early risk factor for stomach cancer.
The researchers' findings also raise concern about a possible link between the drug and stomach cancer in people infected with H. pylori. "The real danger lurks when a person takes metronidazole without the complete complement of drugs that eradicate this bacterium," says Paul S. Hoffman, Ph.D., professor of microbiology and immunology and medicine at Dalhousie University Medical School in Halifax. "When metronidazole is taken alone, it can be activated by one of the bacterium's enzymes to produce hydroxylamine, a mutagen and cancer-causing chemical."
The collaborators describe their findings in the April 14 issue of Molecular Microbiology. Hoffman's graduate student, Avery Goodman, is lead author of the paper.
Metronidazole -- a generic drug sold as Flagyl, MetroGel and Protostat -- is prescribed for dental abscesses, certain vaginal infections and conditions where anaerobic bacteria or protozoan parasites are suspected. It also is the key component in combination therapies for peptic ulcer disease. But between 10 percent and 30 percent of H. pylori strains in the United States and Western Europe are metronidazole-resistant. In developing countries, the proportion may be as high as 80 percent. This resistance is the most common reason for treatment failure, renewal of infection and recurrence of peptic ulcers and other stomach lesions.
The researchers discovered that metronidazole resistance results from
mutation in a gene called rdxA. This gene codes for one of the nitro
Contact: Linda Sage
Washington University School of Medicine