[Clinical and laboratory significance of inducible beta-lactamases]

Many species of bacteria have inducible expression of beta-lactamase and the enzyme production in these bacteria is normally held at a low level by a repressor mechanism, but in the presence of a beta-lactamase inducer this repression is lifted and enzyme production is greatly increased. Inducible synthesis of beta-lactamase was first described for the gram-positive organism Bacillus licheniformis. After that inducible expression of beta-lactamase was discovered in gram-negative bacteria like Enterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, Morganella morganii, Proteus vulgaris, Serratia spp and Aeromonas spp. Inducible beta-lactamases belong into class I according to Richmond and Sykes. They are chromosomally mediated cephalosporinases. beta-lactam antibiotics differ in their inducing power. Cefoxitin and imipenem are among the strongest inducers. Induction of beta-lactamase caused by these substances can lead to antagonism with other beta-lactam antibiotics if they are used in combination. The most important clinical problem connected with inducible beta-lactamases is the emergence of multiple resistant strains which are associated with therapeutic failures. It is important to distinguish induction from derepression. Induction is a temporary phenomenon in which an inducer interacts with a functional AmpD protein, which consequently prevents complexing of the AmpD and ampR proteins. In contrast, genetic derepression is permanent and results from synthesis of a defective AmpD protein unable to complex with the AmpR protein.