In a second step, nucleophilic attack by a water molecule cleaves the covalent bond between the enzyme and the carbonyl group of the erstwhile beta-lactam.
Unlike the case of beta-lactam antibiotics, the inhibitors act as suicide substrates (tazobactam and sulbactam) which ultimately leads to the degradation of the beta-lactamase.
Thus the spread of bacterial strains expressing metallo beta-lactamases such as the New Delhi metallo-beta-lactamase 1 has engendered considerable concern.
The main classes of β-lactam antibiotics used to treat gram-negative bacterial infections include (in approximate order of intrinsic resistance to cleavage by β-lactamases) penicillins (especially aminopenicillins and ureidopenicillins), 3rd generation cephalosporins, and carbapenems.
They have been found generally to fit well into the active site of many beta-lactamases and have the convenient property of being unable to be hydrolysed, and therefore rendered useless.
This is a favorable drug design over many clinically used competing agents, because most of them, such as clavulanic acid, become hydrolysed, and are therefore only useful for a finite period of time.