Ulcer Bacterium's Drug Resistance Unmasked
Seppa, Nathan, Science News
By any measure, the drug metronidazole is a potent disease fighter. Also known as Flagyl, MetroGel, and Protostat, it knocks out the bacterium Helicobacter pylori, as well as microbes that can cause amoebic dysentery, other intestinal ailments, and some vaginal infections.
In 1985, scientists fingered the spiral-shaped H. pylori as the agent responsible for stomach ulcers and have since relied chiefly on metronidazole in combination with other drugs to battle the illness. H. pylori has proved to be a worthy adversary, however, developing widespread resistance to metronidazole.
Canadian and U.S. researchers have now discovered how some H. pylori infections succumb to metronidazole and others withstand its onslaught.
In a search through H. pylori genes taken from individuals in Peru and Lithuania, where the bacterium is common, the scientists identified genetic sequences that make the microbe drug-resistant and differentiated them from normal sequences.
One of the enzymes made by normal H. pylori converts metronidazole into a harsh chemical called hydroxylamine--a protein-busting, DNA-damaging terror that causes mutations in H. pylori's own genes. The besieged bacterium fights furiously to stem this DNA destruction. "If the rate of DNA damage is higher than the rate of repair, the cell dies," says microbiologist Avery C. Goodwin of Dalhousie University in Halifax, Nova Scotia.
Bacteria that escape the chemical reaper often have genetic mutations. If the gene encoding the enzyme that acts on metronidazole is damaged or destroyed, the bacterium becomes resistant to the drug. He and his colleagues report the findings in the April 14 Molecular Microbiology.
"This goes a long way toward helping us to understand metronidazole resistance in H. pylori," says Martin J. Blaser, a microbiologist at Vanderbilt University in Nashville. …