Notre Dame researchers uncover keys to antibiotic resistance in MRSA | News | Notre Dame News | University of Notre Dame Skip To Content Skip To Navigation Skip To Search University of Notre Dame Notre Dame News Experts ND in the News Subscribe About Us Home Contact Search Menu Home › News › Notre Dame researchers uncover keys to antibiotic resistance in MRSA Notre Dame researchers uncover keys to antibiotic resistance in MRSA Published: October 03, 2013 Author: Marissa Gebhard Methicillin-resistant Staphylococcus aureus (MRSA) is shown in the background (in gray). This figure depicts domains and key ligands of the penicillin binding protein 2a — a key resistance enzyme. The red molecule on the right is ceftaroline, a drug recently approved by the FDA. University of Notre Dame researchers Shahriar Mobashery, Mayland Chang, their team members, 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.) Mobashery, Chang and Juan Hermoso at CSIC, the Spanish Research Council, document that an allosteric trigger by a fragment of the cell wall at a distance of 60 Ångstroms (6 nanometers) activates a set of conformational changes that culminates in the opening of the active site from a closed conformation, enabling catalysis for the physiological role of the enzyme. They also document that the new beta-lactam antibiotic ceftaroline, recently approved by the Food and Drug Administration, is able to bind to the allosteric domain and trigger the same allosteric opening of the active site. This subversion of the allosteric control allows another molecule of ceftaroline to access the active site, which inhibits the function of the enzyme, leading to cell death by MRSA. This mechanism of action for the antibiotic is unprecedented and offers important insights for design of future drugs to combat MRSA. MRSA has been a difficult hospital pathogen to control and has emerged in the broader community in the past several years, especially in such places as prisons, locker rooms and nurseries. In the United States alone, the disease infects about 100,000 people and claims the lives of nearly 20,000 people annually. The paper, titled “How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function,” is available online. Contact: Shahriar Mobashery, 574-631-2932, mobashery@nd.edu Posted In: Research Home Experts ND in the News Subscribe About Us Related October 05, 2022 Astrophysicists find evidence for the presence of the first stars October 04, 2022 NIH awards $4 million grant to psychologists researching suicide prevention September 29, 2022 Notre Dame, Ukrainian Catholic University launch three new research grants September 27, 2022 Notre Dame, Trinity College Dublin engineers join to advance novel treatment for cystic fibrosis September 22, 2022 Climate-prepared countries are losing ground, latest ND-GAIN index shows For the Media Contact Office of Public Affairs and Communications Notre Dame News 500 Grace Hall Notre Dame, IN 46556 USA Facebook Twitter Instagram YouTube Pinterest © 2022 University of Notre Dame Search Mobile App News Events Visit Accessibility Facebook Twitter Instagram YouTube LinkedIn