Correlation of the antimicrobial activity of ME1036 with its binding affinities to the penicillin-binding proteins from Streptococcus pneumoniae strains

We have correlated the binding affinities of ME1036, a carbapenem, to the penicillin-binding proteins (PBPs) from Streptococcus pneumoniae strains, with its bactericidal potency against those same strains. Certain mutations in the PBPs from S. pneumonaie strains decrease the binding affinities of beta-lactams for PBPs, which gives rise to clinical resistance to those beta-lactams. ME1036 has been shown to be strongly active against genotypic penicillin-intermediate S. pneumoniae (gPISP) strains and genotypic penicillin-resistant S. pneumoniae (gPRSP) strains that contain more than one mutation in their PBPs, owing to its strong affinity for those PBPs. The Journal of Antibiotics (2011) 64, 741-746; doi:10.1038/ja.2011.76; published online 24 August 2011