University of Notre Dame researchers Shahriar Mobashery and Mayland Chang and their collaborators in Spain have published research results this week that show how methicillin-resistant Staphylococcus aureus (MRSA) regulates the critical crosslinking of its cell wall in the face of beta-lactam antibiotics.
The work, published in the Proceedings of the National Academy of Sciences, reveals the mechanistic basis for how the MRSA bacterium became such a difficult pathogen over the previous 50 years, in which time it spread rapidly across the world. Modern strains of MRSA have become broadly resistant to antibiotics, including beta-lactam antibiotics, such as penicillins. In their report, the researchers disclose the discovery of an allosteric domain in the X-ray structure of the penicillin binding protein 2a of MRSA, the enzyme that carries out the crosslinking reaction. (An allosteric site is a place on the protein where its activity is regulated by the binding of another molecule.)