Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with doripenem.
Davies
Todd A
TA
Johnson and Johnson Pharmaceutical Research and Development, LLC, Room B225, 1000 Route 202, Raritan, NJ 08869, USA. tdavies@prdus.jnj.com
Shang
Wenchi
W
Bush
Karen
K
Flamm
Robert K
RK
D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D015780:Carbapenems / Q000378:metabolism* / Q000494:pharmacology; D000077726:Doripenem; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D046915:Penicillin-Binding Proteins / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism*; D047090:beta-Lactams / Q000378:metabolism* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D029968:Escherichia coli Proteins; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; D000077726:Doripenem