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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.

journal of antibiotics

Structure-activity relations of 5,6-cis carbapenem antibiotics and role of factors determining susceptibility of Escherichia coli to .BETA.-lactam antibiotics.