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.