Dissection of the molecular mechanisms underpinning the threat posed by antibiotic resistance of MRSA to food security

Staphylococci are major causative agents of infectious disease including agricultural livestock mastitis resulting from infection by Staphylococcus aureus. Furthermore, the threat posed by this pathogen to animal health is magnified many fold by the origin of MecA, the resistance determinant responsible for high-level -lactam resistance that typifies MRSA-related infections and the emergence of a novel divergent MecA homologs in cattle. In the former case, it is believed that human MRSA acquired MecA, a monofunctional peptidoglycan transpeptidase from the porcine pathogen Staphylococcus scuri. MecA circumvents the antimicrobial action of -lactams by expression of MecA, which binds these antibiotics so weakly it can perform transpeptidation at otherwise lethal concentrations of them. This project aims to characterise the biochemistry underpinning staphylococcal -lactam resistance and its impact upon antibiotic resistance in the context of food security. The novelty and impact of the project is that if successful, it will allow for the first time, characterization of the enzyme activity of MecA from human and animal pathogens. This will open up the field of staphylococcal antibiotic resistance enzymology allowing enzymatic dissection of the contributions of those components required for methicillin resistance.