Sensitivity of Escherichia coli to various β-lactams is determined by the interplay of outer membrane permeability and degradation by periplasmic β-lactamases: a quantitative predictive treatment

In Gram-negative bacteria, β-lactam antibiotics must overcome two barriers, the outer membrane and the periplasmic β-lactamase, before they reach the targets of their action, penicillin-binding proteins. Although the barrier property of the outer membrane and catalytic property of the β-lactamases have been studied and their significance in creating β-lactam resistance emphasized, the interaction between these two barriers has not been treated quantitatively. Such treatment shows that the sensitivity, to a variety of β-lactams, of the Escherichia coli K-12 cells containing very different levels of chromosomally coded AmpC β-lactamase, or a plasmid-coded TEM-type β-lactamase, can be predicted rather accurately from the penetration rate through the outer membrane and the hydrolysis rate in the periplasm. We further propose a new parameter,‘target access Index', which is a quantitative expression of the result of interaction between the two barriers, and reflects the probability of success for the antibiotic to reach the targets.