Mention resistant staph bacteria, and most people think about the almost invincible strains--officially called methicillin-resistant Staphylococcus aureus (MRSA)--that infect immunocompromised and sick people in hospitals. But in recent years, strains of MRSA that are even more virulent have started spreading outside hospitals and attacking perfectly healthy people (Science, 14 March 2003, p. 1639). Now, researchers say they have discovered how these bugs, which some see as a major public health threat, do their damage.
Typically transmitted in prisons, schools, and locker rooms, "community-associated" MRSA (CA-MRSA) can cause severe infections of skin and soft tissues, pneumonia, and an infection of the blood known as bacteremia, sometimes with deadly results. Why the bacteria are so virulent is unclear. Many believe it's because all CA-MRSA strains carry the gene for a toxin called Panton-Valentine leukocidin (PVL); a recent Science paper suggested that this molecule plays an important role in CA-MRSA-caused pneumonia (Science, 23 February, p. 1130).
But some researchers disagree. "We fight about PVL a lot," says Michael Otto, a researcher at the Rocky Mountain Laboratories, a part of the National Institute of Allergy and Infectious Diseases based in Hamilton, Montana. He wasn't convinced by the Science paper, and he points out that pneumonia occurs in only about 2% of CA-MRSA cases. PVL does not appear to play a role in skin and soft-tissue infections or in bacteremia, Otto says.
Now, his team has found another group of biochemical culprits. They discovered that CA-MRSA strains produce peptides called phenol-soluble modulins (PSMs) in much greater quantities than do hospital strains. When the researchers knocked out the genes for four of these peptides, the so-called α-type PSMs, CA-MRSA bacteria became much milder in mice: Skin infections were less severe, and bacteremia was less often fatal. Apparently, the peptides make the microbe more virulent, the authors concluded.
To find out why PSM-αs are destructive, the researchers added the peptides to human neutrophils--a class of white blood cells that gobbles up bacteria--in the test tube. The neutrophils started collapsing within 5 minutes, and within an hour, many were completely destroyed. Thus, PSMs seem to knock out a major defense system, says Otto, giving MRSA free rein.
"I have no doubt that these peptides contribute to virulence of Staphylococcus aureus," says François Vandenesch of the University of Lyon in France, who has long championed the PVL hypothesis and co-authored the Science paper. But he still believes PVL plays a major role as well.
Henry Chambers, who studies MRSA at the University of California, San Francisco, says that PSMs form "an attractive alternative explanation" to PVL--but both may be important. If Otto's results hold up, Chambers says, they would offer researchers a series of new drug targets.