Inducible β-Lactamases are Principally Responsible for the Naturally Occurring Resistance towards β-Lactam Antibiotics in Proteus vulgaris

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Abstract
The role of inducible chromosomally mediated β-lactamases was studied in 22 Proteus vulgaris isolates by monitoring enzyme induction in the presence of various inducers such as ampicillin, cefalothin, cefuroxime, cefsulodin, 6-aminopenicillanic acid (6-APS), and imipenem. 20 of the isolates exhibited resistance to ampicillin, cefalothin, and cefuroxime, whereas 2 isolates were susceptible to these compounds. In all resistant isolates marked inoculum effects could be observed. Enzyme production proved to be transient, i.e. maximum of enzyme production was achieved after 2 or 3 h. In both sensitive isolates enzyme production did not exceed 0.021 U β-lactamase/mg protein of the cell-free supernatant even after induction with 6-APS or imipenem, whereas it ranged from 0.46 to 6.3 U in the resistant ones. Moreover, enzyme induction was found to be concentration-dependent, as revealed by the extensive study of one of the isolates (No. 4917). Three different enzymes could be distinguished by means of isoelectric focusing with isoelectric points at 7.4, 8.8, and approximately 9.5. In the presence of 2.5 mg/l clavulanic acid even strains known to be strong enzyme producers became as susceptible as the sensitive ones: moreover, the inocolum effect was markedly reduced. These findings make it apparent that it is above all the production of inducible enzymes that is responsible for resistance to β-lactam antibiotics in P. vulgaris.

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