Three Pseudomonas aeruginosa strains which constitutively produced chromosomal (Id, or Sabath and Abraham) beta-lactamase in large amounts were resistant to latamoxef (moxalactam) MICs, 128-256 mg/l). Their beta-lactamase-basal mutants, which produced 1200-18,000-fold less enzyme, were latamoxef-sensitive (MICs, 4-16 mg/l), suggesting that the enzyme caused the resistance of the parent organisms. Latamoxef was a feeble substrate of the enzyme (kcat less than 0.5/min) but reacted to form a stable complex that lacked catalytic activity against benzylpenicillin. The complex was isolated by gel filtration and was shown to be stable to isoelectric focusing, suggesting a covalent link between the enzyme and latamoxef. During incubation the complex underwent a slow breakdown, regenerating active enzyme. This breakdown obeyed first-order kinetics, and the half-life of the inactivated form was 19 +/- 1 min at 37 degrees C. Binding of antibiotic molecules in this complex may contribute to the latamoxef-resistance observed in the beta-lactamase-derepressed strains. This 'covalent trapping' should be distinguished from the 'non-covalent trapping' proposed elsewhere as a general mechanism of beta-lactamase-mediated resistance to reversibly-bound weak-substrate beta-lactams.
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