The β-Lactamases of Gram-Negative Bacteria and their Possible Physiological Role

Abstract

Publisher Summary β -lactamases are the enzymes that are capable of hydrolyzing the β -lactam bond of penicillins and cephalosporins. The reaction catalyzed by β -lactamases with penicillins as substrates includes the rupture of the β -lactam bond to form the corresponding penicilloic acid. However, there is complexity in breakdown of the cephalosporins after β -lactamase action as there is no sporin and the formation of any single product—a fact that invalidates the iodometric assay of cephalosporinase for absolute measurement. Despite the wide and varying specificity, β -lactamases often require the 4-membered azetidinone ring to be condensed either with a thiazolidine (penicillins) or a dihydrothiazine nucleus (cephalosporins). The molecular basis of the resistance of Gram-negative bacteria to β -lactam antibiotics is very different from their Gram-positive counterparts. Some of the possible physiological role recognized for β -lactamases includes—namely, (1) hydrolysis of β -lactam antibiotics when required and (2) destruction of β -lactam antibiotics. The role of protecting the organisms that produce β -lactamases against the deleterious effects of penicillins and cephalosporins can often provide a major obstacle to the successful use of β -lactam antibiotics for therapy.