Chromosomal beta-lactamase expression and resistance to beta-lactam antibiotics in Proteus vulgaris and Morganella morganii

Abstract

Indole-positive members of the Proteeae usually have inducible expression of chromosomal beta-lactamases. Mutants with stably derepressed beta-lactamase expression occur in inducible populations at frequencies in the range of 10(-6) to 10(-8). The contribution of these beta-lactamases to drug resistance was examined in Morganella morganii and Proteus vulgaris. The M. morganii enzyme was a high-molecular-weight (49,000) class I cephalosporinase with low Vmax rates for ampicillin, carbenicillin, and and broad-spectrum cephalosporins. The P. vulgaris enzyme had a lower molecular weight (32,000) and high Vmax rates for ampicillin, cephaloridine, cefotaxime, and ceftriaxone. Imipenem and cefoxitin inactivated the P. vulgaris enzyme but were low-Vmax, low-Km substrates for that of M. morganii. Despite these differences, the two beta-lactamases caused similar resistance profiles. Ampicillin and cephaloridine were strong inducers for both species, and beta-lactamase-inducible strains and their stably derepressed mutants were resistant, whereas basal mutants (those with low-level uninducible beta-lactamase) were susceptible to these two compounds. Mezlocillin, cefotaxime, ceftriaxone, and (usually) carbenicillin were almost equally active against beta-lactamase-inducible organisms and their basal mutants, but were less active against stably derepressed mutants. This behavior reflected the beta-lactamase lability of these drugs, coupled with their weak inducer activity below the MIC. Carbenicillin was a labile strong inducer for a single P. vulgaris strain, and inducible enzyme was protective against the drug in this atypical organism. Cefoxitin and imipenem, both strong inducers below the MIC, were almost equally active against beta-lactamase-inducible organisms and their basal and stably derepressed mutants.