Evolution and spread of SHV extended-spectrum β-lactamases in gram-negative bacteria

Abstract

Resistance to β-lactam antibiotics has been a problem for as long as these drugs have been used in clinical practice. In clinically significant bacteria the most important mechanism of resistance is the production of one or more β-lactamases, enzymes that hydrolyse the β-lactam bond characteristic of this family of antibiotics. Prominent among the β-lactamases produced by the Enterobacteriaceae is the SHV family. The first reported SHV β-lactamase had a narrow spectrum of activity. By the accumulation of point mutations at sites that affect the active site of the enzyme, a family of derivatives of SHV-1 has evolved. Derivatives of SHV-1 either have an extended spectrum of activity, capable of inactivating third-generation cephalosporins, or are resistant to β-lactamase inhibitors. This review describes the evolution and spread of the SHV family of β-lactamases, introducing the structure-function analysis made possible by DNA sequence analysis. It also reviews the methods used to characterize members of this family of β-lactamases, indicating some of the difficulties involved.