Some of the most aggressive antibiotic-resistant staph infections gain their advantage with a molecule that punctures the immune cells trying to fight off the bacteria, scientists have discovered. Understanding the role of this molecule in methicillin-resistant Staphylococcus aureus (MRSA) could lead to new therapies for the notoriously hard-to-treat, and sometimes fatal, skin infection.
Staph bacteria are ubiquitous but aren’t dangerous unless they seep into an open wound. Even then, antibiotics will usually stop the infection. But some strains of staph that infect hospital patients with weakened immune systems have become resistant to all standard antibiotics, including methicillin.
Now, a newer strain of the flesh-eating disease has swept through schools, day care centers, health club locker rooms, and prisons. So-called community-associated MRSA (CA-MRSA) typically afflicts healthy people because it’s especially effective at causing infections in the first place. For now, it’s resistant only to methicillin, but scientists fear that it will become resistant to other antibiotics.
In the Oct. 17 Journal of the American Medical Association, Monina Klevens of the Centers for Disease Control and Prevention in Atlanta and her colleagues gave the first statistics on just how widespread MRSA has become. The researchers estimated that 94,360 cases occurred in 2005, leading to 18,650 deaths. They argued that these numbers are on the rise, particularly outside the hospital setting.
In a separate study, Michael Otto of the National Institute of Allergy and Infectious Diseases and his colleagues found a molecule involved in CA-MRSA’s success.
While studying small molecules that help a different bacterium, Staphylococcus epidermidis, fight its host, the scientists decided to check whether MRSA carried a similar molecule. They found that CA-MRSA had much more of a protein called phenol-soluble modulin (PSM) than the less virulent MRSA strains associated with hospitals had.
“Different bacteria have different strategies to attack the human immune system,” explains Otto. S. aureus “seems to have a lot of strategies, it’s really good at that.”
The team elucidated PSM’s importance by isolating the protein and adding it to white blood cells called neutrophils, which usually engulf and destroy bacteria that enter the body. PSM molecules destroyed neutrophils by forming pores on the cells, letting their contents leak out.
Otto’s team then injected mice with a form of MRSA engineered to lack the PSM gene. After a day, those mice were still alive, but more than half of a group of mice exposed to normal MRSA had died. The results appear online and in an upcoming Nature Medicine.
Until last year, most scientists had focused on a different protein, called Panton-Valentine leukocidin (PVL), as the key to CA-MRSA’s deadliness, because it’s far more abundant in CA-MRSA than in the hospital-associated strain. But Otto and his colleagues showed that deleting PVL from the bacterium does not make it less deadly.
Lindsey Shaw of the University of South Florida in Tampa says that the jury is still out on PVL, and while he calls the findings on PSM “incredibly important,” he also notes that it doesn’t explain the virulence of all strains of MRSA.
“There are strains that don’t make these molecules, and they still kill people,” he says.
Both Shaw and Otto note that the ability of staph bacteria to adapt quickly to new environments is what allows different strains to express different molecules and become so dangerous.
“This is just another niche it’s exploited,” says Shaw. “Some shift may have happened where some strains started [making PSM] and it turned out to be favorable.”