Journal: Antimicrobial Agents and Chemotherapy

Article Title: First Penicillin-Binding Protein Occupancy Patterns of β-Lactams and β-Lactamase Inhibitors in Klebsiella pneumoniae

doi: 10.1128/AAC.00282-18

Figure Lengend Snippet: Principal component analysis of the log-transformed PBP IC50 data for our 13 tested compounds in two K. pneumoniae strains. The plot shows the clustering of compounds according to their positions on the first and second eigenvector. These two vectors explained 86.5% of the total variance. Compounds were grouped into two general clusters. The first cluster contained β-lactams that primarily targeted PBP3 but differed in their secondary targets. The second cluster was comprised of compounds that primarily targeted PBP2 or both PBPs 2 and 4. Of note, among compounds in the second cluster, the carbapenems, amoxicillin, and mecillinam had substantially lower IC50 for their primary targets than the β-lactamase inhibitors. Symbols for β-lactamase inhibitors are smaller due to their much higher IC50 for their primary PBP target relative to the primary PBP target IC50 of the β-lactams.

Article Snippet: Biapenem was purchased from TRC Canada (Toronto, Ontario, Canada); doripenem and avibactam were from MedChem Express (Monmouth Junction, NJ); imipenem and meropenem were from AK Scientific (Union City, CA); sulbactam was from TCI America (Portland, OR); tazobactam, amoxicillin, piperacillin, aztreonam, cefepime, and cefsulodin were from Chem-Impex International, Inc. (Wood Dale, IL); and mecillinam was from Molekula (Newcastle Upon Tyne, United Kingdom).

Techniques: Transformation Assay