Structure-activity relations of 5,6-cis carbapenem antibiotics and role of factors determining susceptibility of Escherichia coli to beta-lactam antibiotics.
The antibacterial activities of twelve 5,6-cis carbapenem antibiotics, including four semisynthetic derivatives of C-19393 H2 and S2, against 15 microorganisms were examined, and their structure-activity relations are discussed in relation to minimum inhibitory concentrations against Staphylococcus aureus and Escherichia coli as a Gram-positive and a Gram-negative standard strain, respectively. The contribution of chromosomal beta-lactamase (amp C), permeability barrier, and penicillin-binding protein (PBP) 1B to the resistance of E. coli to these carbapenem antibiotics was examined using mutants lacking each of these cellular components. The beta-lactamase was not involved in the resistance. These antibiotics easily permeated the outer membrane. A PBP 1B-defective mutant was supersensitive to these carbapenem antibiotics and to other types of beta-lactam antibiotics.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases