Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae

Abstract

Ceftobiprole exhibited tight binding to PBP2a in methicillin-resistant Staphylococcus aureus, PBP2x in penicillin-resistant Streptococcus pneumoniae, and PBP3 and other essential penicillin-binding proteins in methicillin-susceptible S. aureus, Escherichia coli, and Pseudomonas aeruginosa. Ceftobiprole also bound well to PBP2 in the latter organisms, contributing to the broad-spectrum antibacterial activity against gram-negative and gram-positive bacteria.

FIG. 1.

P. aeruginosa PAO1 grown for 1.5 h in (A) nutrient broth alone (control) or (B) nutrient broth containing 1 μg/ml ceftobiprole (1× MIC). Magnification, ×1,000.

FIG. 2.

Affinity of PBP2a from S. aureus 3726 for ceftobiprole (BPR) or ceftazidime (CAZ). All samples except “C” were initially preincubated with 1 mg/ml of clavulanic acid to saturate all PBPs except PBP2a. For competition assays, ceftobiprole or ceftazidime was added at the indicated concentrations, followed by labeling with Bocillin FL. IC₅₀ values were calculated by 50% inhibition of Bocillin FL binding compared to the no-drug (0 μg/ml) sample. Lane “C” contains PBPs labeled only with Bocillin FL in order to visualize all PBPs.