Pentapeptide and Beta-lactam Activity Against Recombinant PBP2a from Methicillin-resistant Staphylococcus Aureus.
Dr. Ken Cornell
Methicillin-resistant Staphylococcus aureus causes serious skin infections, which if left untreated can result in sepsis and death. In the U.S., MRSA is associatied with both hospital- and community- acquired infections, and is prevalent in common shared areas such as gym facilities and locker rooms, allowing for massive distribution and contact within the general public, thus increasing the urgency for new drug treatment. / MRSA is known as a “superbug” due to the difficulty of treatment utilizing current available antibiotics known as beta-lactams (such as methacillin, oxacillin and penicillin). One drug resistance mechanism for MRSA resides within the mutated Penicillin-Binding-Protein 2a (PBP2a), which is an essential component for cell wall synthesis and survival. / A new panel of hydrophobic pentapeptides have recently been shown to synergize oxacillin action against MRSA, suggesting that these peptides influence the interaction of PBP2a with the beta lactam antibiotic. This provides a new direction for drug development that focuses on antibiotics that further the action of currently used therapeutics. To further explore this paradigm, the gene for PBP2a has been cloned and expressed from MRSA. Interactions of oxacillin and pentapeptide with PBP2a are being studied to further quantify the ability of the peptides to enhance beta lactam action against this serious pathogen.