A model system to demonstrate that beta-lactamase-associated antibiotic trapping could be a potential means of resistance.
Addition of beta-lactamase to cultures of antibiotic-sensitive Escherichia coli protected the bacteria against lysis induced by either a hydrolyzable (cephalothin) or relatively nonhydrolyzable (ceftriaxone) cephalosporin. The later addition of a nonhydrolyzable, non-lysis-inducing beta-lactam antibiotic (oxacillin), which had a higher affinity for the beta-lactamase than ceftriaxone, allowed the reversal of the protection and the onset of lysis. These results suggest that trapping of the antibiotic by the enzyme, without significant hydrolysis, is a reversible process that may play a role in the resistance of some gram-negative bacteria to third-generation cephalosporins.
D002439:Cefotaxime / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002443:Ceftriaxone; D002511:Cephalosporins / Q000494:pharmacology*; D002512:Cephalothin / Q000378:metabolism / Q000494:pharmacology; D004754:Enterobacter / Q000187:drug effects* / Q000201:enzymology; D004755:Enterobacteriaceae / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects*; D010068:Oxacillin / Q000378:metabolism / Q000494:pharmacology*; D010403:Penicillin Resistance; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism*
D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; D002443:Ceftriaxone; D001618:beta-Lactamases; D002439:Cefotaxime; D002512:Cephalothin; D010068:Oxacillin