The rates of hydrolysis of carbenicillin and of other penicillins and cephalosporins by nine different P-lactamase preparations obtained from Gram-negative bacteria were compared. Enzymes produced by Klebsiella strains, most active against penicillins, as well as P-lactamases synthesized by Escherichia coli and Proteus tnirabilis strains hydrolysed carbenicillin, although at relatively lower rates than ampicillin or cephaloridine. In contrast, carbenicillin was extremely resistant to /3-lactamases with a predominant cephalosporinase activity as produced by Pseudomonus aeruginosa, Proteus vulgaris and Enterobacter strains. The cephalosporin P-lactamases activity of these enzymes was inhibited by carbenicillin. A considerably increased enzymic activity observed in one strain of Pseudomonas ueruginosa when grown in the presence of carbenicillin or other P-lactam antibiotics was unable to destroy carbenicillin to any measurable extent. A possible permeability barrier to carbenicillin has been demonstrated in some strains.
A plasmid, derived from a naturally occurring strain of Proteus mirabilis, conferred resistance to cephalosporins, apparently mediated by a beta-lactamase indistinguishable from that determined by the chromosomal gene of Escherichia coli K-12. There was evidence for a recombination event between the wild-type plasmid and a defective F factor (Fsp) in the Escherichia coli K-12 culture in which it was stored.
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