The long-dreaded superbug surfaced on a summer Friday in 2002. The new strain of Staphylococcus aureus, cultured from a diabetes patient in Detroit, had developed resistance to vancomycin, one of the few antibiotics left that reliably kills staph. Now, a study shows how the microbe became a menace.
S. aureus lives on the skin and in the noses of healthy people, causing nothing worse than pimples and boils. But in hospitalized patients, it causes tens of thousands of infections each year, including serious and sometimes fatal surgical-wound infections, bloodstream infections, and pneumonia. The microbe has learned to evade one antibiotic after another, and by the late 1980s, vancomycin was the drug of last resort.
When the Detroit vancomycin-resistant S. aureus (VRSA) strain appeared, detective work began. Doctors isolated two nearly identical strains from the patient. The only difference appeared to be vancomycin resistance or susceptibility. Doctors also cultured vancomycin-resistant Enterococcus faecalis from the patient's foot ulcers. Circular loops of DNA called plasmids from the VRSA and E. faecalis strains, but not the susceptible S. aureus strain, had a gene called vanA that wards off vancomycin. That suggested that the drug-resistance gene had jumped species, Weigel says.
To see how it made the jump, microbiologists Linda Weigel and Fred Tenover of CDC and colleagues checked the plasmids for a mobile genetic element called a transposon, a snippet of DNA that can jump out of one plasmid and worm its way into another. Indeed, both vancomycin-resistant strains hosted a plasmid with a transposon containing vanA.
The results suggest that E. faecalis in the woman's ulcer sidled up to S. aureus and passed along its resistance plasmid, the researchers report in the in the 28 November issue of Science. Enzymes in S. aureus seem to have destroyed the foreign E. faecalis plasmid, but before that happened, the transposon jumped, like a rat escaping a sinking ship, and infiltrated the S. aureus's resident plasmid to create a new hybrid. That created a nasty new S. aureus strain that can spread readily in hospitals, resist almost all the drugs available to kill it, and share its weapons with S. aureus cousins that remain vulnerable to vancomycin. “What we've isolated is really the triple threat,” Tenover says.
Two antibiotics, linezolid (Zyvox) and quinupristin/dalfopristin (Synercid), still stop VRSA, says microbiologist Donald Low of the University of Toronto. But it's important that drug companies step up efforts to develop alternatives, he says: “Right now we've got something in our back pocket, but that could change rapidly.”
CDC fact sheet on VRSA