Journal of Antimicrobial Chemotherapy (1999) 44, 309-318
© 1999 The British Society for Antimicrobial Chemotherapy
Review |
Evolution and spread of SHV extended-spectrum ß-lactamases in Gram-negative bacteria
Division of Microbiology, School of Biochemistry and Molecular Biology, and the Antimicrobial Research Centre, University of Leeds, Leeds LS2 9JT, UK
Resistance to ß-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 ß-lactamases, enzymes that hydrolyse the ß-lactam bond characteristic of this family of antibiotics. Prominent among the ß-lactamases produced by the Enterobacteriaceae is the SHV family. The first reported SHV ß-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 ß-lactamase inhibitors. This review describes the evolution and spread of the SHV family of ß-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 ß-lactamases, indicating some of the difficulties involved.
* Tel: +44-113-233-5592; Fax: +44-113-233-5647; E-mail: j.heritage{at}leeds.ac.uk
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