Birth of a Supergerm

Scientists discover gene exchange that leads to drug-resistant bug

FRIDAY, Nov. 28, 2003 (HealthDayNews) -- Scientists say they've determined the genetic trick by which a dangerous germ acquired resistance to a highly potent antibiotic, earning itself "supergerm" status in the process.

The bug is Staphylococcus aureus, a leading cause of skin and bloodstream infections; the drug is vancomycin. Until recently, vancomycin was the staph-fighting equivalent of the Powell Doctrine -- overwhelming force against a vulnerable enemy.

But given the history of other antibiotics, it was only a matter of time before the bug would evolve resistance to vancomycin. The first shot was heard in 1997, in Japan, with a bug that had modest immunity to the drug. That was followed by two more in the United States earlier this decade -- but in both cases the staph had full resistance to vancomycin.

The latest study, reported in the Nov. 28 issue of Science, analyzed a sample from one of the U.S. cases, a supergerm discovered last year in a 40-year-old Michigan kidney patient.

Examining the genetic makeup of the supergerm, researchers learned that it had acquired a key resistance gene, called vanA, from an unrelated microbe. The microbe, Enterococcus faecalis, has been hardened to vancomycin since at least 1988.

What makes the feat especially interesting, the researchers say, is that it happened within the patient herself.

Fred Tenover, a drug resistance expert at the Centers for Disease Control and Prevention and leader of the study, says the woman presented a "perfect storm" for breeding the supergerm. She had a history of taking vancomycin, a history of vancomycin-resistant E. faecalis, and was being treated for infection with a strain of staph resistant to the drug methicillin.

At some point an E. faecalis -- which is known to be a "promiscuous" gene swapper, Tenover says -- mated, or conjugated, its genetic material with that of a staph bug. The staph bug added vanA to a doughnut-shaped array of genetic material, known as a plasmid, that it already had and discarded the rest of the donated genes.

In the Japanese example of vancomycin-resistant staph (VRSA), the organism evolved to create a cell-well that binds up the drug and keeps it from penetrating. In the Michigan case, the addition of vanA allowed the germ to build a cell wall that is effectively invisible to the antibiotic, Tenover says.

Dr. Peter Appelbaum is an infection expert at Penn State's Hershey Medical Center, whose lab isolated the other U.S. case of VRSA. That strain also had a plasmid that confers resistance to vancomycin, along with other drugs.

But how it got there is still a mystery. "We don't know how our patient got it," Appelbaum says.

What is clear, Appelbaum adds, is that the two cases of VRSA in the United States are almost certainly not the only ones around.

"Nobody is going to tell me that this thing is not present in other places," says Appelbaum, who points to the chronic leg and foot ulcers of diabetics as a likely breeding ground for the supergerms.

Although S. aureus can now resist vancomycin, it remains fully susceptible to other antibiotics available to doctors. However, scientists fear that overuse of these drugs, coupled with the germ's natural ability to adapt its way out of harm, will eventually reduce their effectiveness, too.

Knowing how VRSA was born could help scientists design new antibiotics to kill it, Tenover says.

Perhaps most surprising about the emergence of VRSA is why it took so long, Tenover adds.

Scientists began expecting its arrival two decades ago, and when no cases cropped up after about 10 years, they began to wonder if the organism faced a biological hurdle that prevented it from adapting around the drug.

"We now know that there are no such barriers," Tenover says.

More information

For more on S. aureus, try the Food and Drug Administration or the Centers for Disease Control and Prevention.

SOURCES: Fred Tenover, Ph.D., associate director, laboratory science, Division of Health Care Quality Promotion, U.S. Centers for Disease Control and Prevention, Atlanta; Peter C. Appelbaum, M.D., professor of clinical pathology, Penn State Milton S. Hershey Medical Center; Nov. 28, 2003, Science
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