1887

Abstract

SUMMARY: The quantities of penicillin-binding proteins (PBPs), and sensitivity to extended-spectrum β-lactams, were measured in isogenic strains of with high (HR) and low (LR) resistance to extended-spectrum β-lactam antibiotics and with constitutively overproduced chromosomal β-lactamase in the periplasm. The binding of structurally different β-lactams to PBPs in growing resistant bacteria was determined quantitatively. In HR, the amounts of PBPs 3 and 6 were, respectively, 1·5 and 2 times those in strain LR and in sensitive reference strains. Sensitivities of the essential PBPs in LR and HR to the tested β-lactams were identical. Only a single target, PBP 3, was highly sensitive to cefotaxime, ceftazidime and aztreonam. In contrast, three PBPs (2, 1A and 3) were highly sensitive to imipenem. In growing HR and LR, all antibiotics, even at fractions of their minimal growth inhibitory concentrations (MICs), bound extensively to those PBPs which were highly sensitive to them. Thus, overproduced β-lactamase did not prevent PBP-β-lactam interaction. Only at or above their (high) MICs did cefotaxime, ceftazidime and aztreonam bind to multiple targets. Growth inhibition of the otherwise highly resistant HR at the lower MIC of imipenem was correlated with the binding of this antibiotic to multiple, highly sensitive targets in the bacteria. Killing of the bacteria by inactivation of multiple targets was suggested. This assumption was supported by the synergistic killing of HR bacteria by combinations of the PBP-2-specific mecillinam with PBP-3-specific β-lactams.

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/content/journal/micro/10.1099/00221287-137-2-243
1991-02-01
2019-11-21
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http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-137-2-243
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