Contribution of chromosomal beta-lactamases to beta-lactam resistance in enterobacteria

The two most important factors determining the level of beta-lactam resistance to novel cephalosporins in gram-negative enterobacteria are the chromosomal class C beta-lactamases, which have high affinity for these compounds, and the outer membrane permeability barrier. The individual importance of these factors and the interactions between them are discussed. Wild-type strains carry a chromosomal gene, ampC, encoding class C beta-lactamases. Expression from this gene is normally low, but it can in some species be induced by beta-lactam agents and related compounds. The current knowledge on the molecular mechanism governing both inducible and constitutive beta-lactamase synthesis is reviewed. Insight into these mechanisms explains why mutations leading to high-level enzyme over-production and beta-lactam resistance are much more frequent in species with a normally inducible beta-lactamase gene than in other gram-negative bacteria.