TEM-DERIVED AND SHV-DERIVED EXTENDED-SPECTRUM BETA-LACTAMASES - RELATIONSHIP BETWEEN SELECTION, STRUCTURE AND FUNCTION

The later-generation cephalosporins were developed to overcome beta-la ctamases which conferred resistance to earlier beta-lactam drugs. With in two years of their clinical introduction, the ubiquitous TEM and SH V plasmid-encoded beta-lactamase genes underwent simple point mutation s that changed key amino acids around the active site of the protein a nd enabled the enzyme to bind and hydrolyse these new drugs. Successiv e mutations interacted in concert, radically increasing the enzymes' a bilities to bind and confer resistance to later-generation cephalospor ins. These modified enzymes have been classified in three groups, base d on activity, and altered functions have been correlated with changes in the enzyme structure.