Combatting antibiotic resistance in MRSA: the structural biology of beta-lactam resistance regulation by the protease domain of Staphylococcus aureus protein BlaR1

Antibiotic resistant infections are becoming more widespread, posing serious threats to human health. For example, Staphylococcus aureus bacteria are common on the skin of healthy people, but can cause serious infections if they penetrate the skin and enter the body. The antibiotic, methicillin, effectively treats most “staph” infections, but some bacteria have developed a resistance. As a result, MRSA (methicillin-resistant staphylococcus aureus) outbreaks can be life-threatening in hospital wards, especially for patients with compromised immune systems. Even more worrisome is that new strains of MRSA that can infect and harm otherwise healthy people – called ‘community MRSA’ – are on the rise across Canada. Michael Gretes is investigating how MRSA bacteria turn their resistance genes off and on using two proteins. The first protein keeps the resistance turned off. Another protein has a scissor-like part. With no antibiotics around, the scissors are closed. When penicillin or methicillin is administered to try to kill the bacteria, the scissors receive a signal to cut the first protein, turning the antibiotic resistant genes on. Michael is x-raying protein crystals to determine how the scissor functions. This information may lead to new drugs to keep the scissors locked, which could be combined with antibiotics for patients with antibiotic resistant infections.