Structure-Activity relations of 5,6-Cis carbapenem antibiotics and role of factors determining susceptibility of escherichia coli to β-Lactam antibiotics

Abstract

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 Grampositive and a Gram-negative standard strain, respectively. The contribution of chromosomal β-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 β-lactamase was not involved in the resistance. These antibiotics easily permeated the outer membrane. A PBP IB-defective mutant was supersensitive to these carbapenem antibiotics and to other types of β-lactam antibiotics. © 1984, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.