ABSTRACT

Introduction ........................................................................................................ 104 Classi cation of β-Lactamases .......................................................................... 104 Origin of β-Lactamases ..................................................................................... 105 Class A β-Lactamases ....................................................................................... 106 Class B β-Lactamases ........................................................................................ 114 Class C β-Lactamases ........................................................................................ 116 Class D β-Lactamases ....................................................................................... 119 Perspectives ........................................................................................................ 121 Acknowledgments .............................................................................................. 122 References .......................................................................................................... 122

The catalytic function of β-lactamases is the primary cause of resistance to β-lactam antibiotics. These enzymes hydrolyze the β-lactam ring of these versatile antibiotics, a process that inactivates the drugs. Over 470 β-lactamases are known that are grouped into four distinct functional classes (classes A, B, C, and D). The members of each class operate by distinct catalytic mechanisms. A series of recently discovered β-lactamases exhibit wide breadth for their substrate preferences, which often include penicillins, cephalosporins, and carbapenems among other substrates. These so-called extended-spectrum β-lactamases (ESBLs) are being identi ed among all classes of β-lactamases. The breadth of phenotypic traits for each of these enzymes collectively includes all known types of β-lactam antibiotics. The global distribution

of the pathogens that harbor these various enzymes is suf ciently different at the present that obsolescence of β-lactam antibiotics has not happened to date. This chapter discusses the various properties of these microbial enzymes.