Speculation regarding the target of P2As. GraS, a histidine kinase, is known to regulate several pathways, and is also associated with resistance to β-lactams and other cell wall-acting antimicrobials. While inhibition of GraSR signaling reduces resistance to cefuroxime, which is penicillinase-sensitive, it does not affect oxacillin resistance. This profile fits our observations from Table , where we have shown an enhancement of penicillinase-sensitive penicillin G, but not oxacillin. Unfortunately, the graS and graR k/o mutants are unavailable in the NTML library. It would be interesting to model the interactions of GraS with 1, 2 and 3, but a BLAST search clearly demonstrated that no appropriate templates are available: the closest structure was WalK from Bacillus subtilis, but it had <30% sequence identity to the GraS kinase domain, albeit it was higher in the ATP-binding pocket. The complexity of modeling interactions of chemicals with homology models coupled with absence of experimental confirmation of interaction with GraS and P2As makes it impractical to include those results in this manuscript, but we hope to address this hypothesis in future.