Contribution of beta-lactamases to bacterial resistance and mechanisms to inhibit beta-lactamases.
Resistance of bacteria to beta-lactam antibiotics has become a serious problem in the past several decades. Virtually all Staphylococcus aureus, and many Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Enterobacteriaceae, and Bacteroides species possess beta-lactamases that hydrolyze penicillins and cephalosporins. The most common plasmid-mediated beta-lactamase is the TEM enzyme (Richmond-Sykes type IIIa), which is present in Hemophilus, Neisseria, and Enterobacteriaceae. One technique to overcome bacterial resistance has been the development of beta-lactamase inhibitors. Clavulanic acid is a beta-lactamase inhibitor that inhibits the beta-lactamases of S. aureus, Hemophilus, Neisseria, Branhamella, Eschericia coli, Klebsiella, and Bacteroides. Clavulanate acts as a "suicide" inhibitor, forming a stable enzyme complex that binds to serine at the active site of the enzyme. Clavulanate readily crosses the outer cell wall of most Enterobacteriaceae to interact with beta-lactamases in the periplasmic space. Clavulanate does not inhibit beta-lactamases such as the Richmond-Sykes type I enzymes found in Pseudomonas aeruginosa, Enterobacter, and Citrobacter species, which are inducible enzymes that function primarily as cephalosporinases.
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000201:enzymology*; D055598:Chemical Phenomena; D002621:Chemistry; D004352:Drug Resistance, Microbial; D004790:Enzyme Induction; D006090:Gram-Negative Bacteria / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000201:enzymology; D007700:Kinetics; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000145:classification / Q000502:physiology*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases