Our chemicals re-sensitize MRSA to penicillin G, but not penicillinase-resistant antimicrobials such as oxacillin. Recent literature reports on enhancer discovery have focused on 2 central pathways controlling oxacillin resistance: A eukaryotic-like serine/threonine kinase called Stk1 and a histidine kinase called VraS. We will show that P2As do not function via these pathways, suggesting their target is novel. Our finding that P2As reduce the MIC of penicillin G, but not oxacillin and other penicillinaseinsensitive β-lactam antimicrobials, demonstrates the feasibility of bringing the oldest of our arsenal of antimicrobials back into use.