Doctors first identified methicillin-resistant Staphylococcus aureus (MRSA) bacteria in the 1960s and hospitals have been fighting to control their spread ever since. MRSA carry a unique protein called PBP 2a on the cell membrane that plays a key role in helping to defend against antibiotics. In February, Shahriar Mobashery of Notre Dame University and his colleagues identified specific components of the bacterial cell wall that interact with PBP 2a to form a chemical barricade. The team has now made three new synthetic antibiotics based on cephalosporin, a close relative of penicillin. The compounds contain protein components that mimic the crucial parts of the cell wall that cooperate with PBP 2a, which leads to its deactivation and forces the bacterium to succumb to the medication. "We are the first to demonstrate this unique strategy," Mobashery says, "which could provide a new line of defense against the growing problem of antibiotic resistance."
The scientists tested the novel compounds against vancomycin-resistant MRSA and found that they successfully killed the bacteria, whereas a class of conventional antibiotics known as beta-lactams did not. One of the compounds has since begun Phase I clinical studies, but it will take more studies and time before it can be widely marketed. "As scientists, we're trying to stay one step ahead of the bacteria," Mobashery notes. "The more strategies there are to fight resistance, the better."