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

Resistance to beta-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 beta-lactamases, enzymes that hydrolyse the beta-lactam bond charact...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 1999-09, Vol.44 (3), p.309-318
Main Authors: HERITAGE, J, M'ZALI, F. H, GASCOYNE-BINZI, D, HAWKEY, P. M
Format: Article
Language:English
Subjects:
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Bacteriology
beta-Lactam Resistance - genetics
beta-Lactamases - classification
beta-Lactamases - genetics
Biological and medical sciences
Cephalosporins - pharmacology
Enterobacteriaceae
Evolution, Molecular
Fundamental and applied biological sciences. Psychology
Gram-Negative Bacteria - enzymology
Gram-Negative Bacteria - genetics
Humans
Klebsiella pneumoniae - enzymology
Medical sciences
Metabolism. Enzymes
Microbiology
Pharmacology. Drug treatments
Structure-Activity Relationship
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Summary:Resistance to beta-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 beta-lactamases, enzymes that hydrolyse the beta-lactam bond characteristic of this family of antibiotics. Prominent among the beta-lactamases produced by the Enterobacteriaceae is the SHV family. The first reported SHV beta-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 beta-lactamase inhibitors. This review describes the evolution and spread of the SHV family of beta-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 beta-lactamases, indicating some of the difficulties involved.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/44.3.309