Recent developments in beta-lactamase research and their implications for the future.
beta-Lactamases, major determinants of bacterial resistance to beta-lactam antibiotics, can be classified into specific molecular classes following identification of active-site amino acid or nucleotide sequences. The use of gene probes for epidemiologic purposes is becoming commoner. A semiempirical classification scheme has been proposed using substrate profiles and inhibition by clavulanic acid and aztreonam as criteria. Class 1 cephalosporinases are potently inhibited by aztreonam but poorly inhibited by clavulanate, whereas class 2 penicillinases and broad-spectrum beta-lactamases have very poor affinities for aztreonam but are inhibited by clavulanic acid. Class 3 beta-lactamases include the metalloenzymes. Resistance to beta-lactam antibiotics can be related to many beta-lactamase-mediated phenomena, including increased frequency of beta-lactamase production in clinical isolates, wider distribution of beta-lactamase-mediating plasmids, production of multiple beta-lactamases, induction of chromosomal class 1 cephalosporinases, selection of depressed mutants for production of class 1 enzymes, leakage of beta-lactamase from gram-negative organisms, functions of penicillin-binding proteins as beta-lactamases, and identification of novel beta-lactamases.
Bush
K
K
Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology*; D004352:Drug Resistance, Microbial; D001618:beta-Lactamases / Q000032:analysis* / Q000145:classification; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases