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

Abstract
The antibacterial activities of 12 5,6-cis carbapenem antibiotics, including 4 semisynthetic derivatives of C-19393 H2 and S2, against 15 bacteria were examined. Their structure-activity relations are dicussed in relation to minimum inhibitory concentrations against Staphylococcus aureus and E. coli as a gram-positive and a gram-negative standard strain, respectively. The contribution of chromosome .beta.-lactamase (ampc), 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.

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