alexa Plasmid-mediated resistance to third-generation cephalosporins caused by point mutations in TEM-type penicillinase genes.


Journal of Neonatal Biology

Author(s): Sougakoff W, Goussard S, Gerbaud G, Courvalin P

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Abstract Infections due to strains of Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii resistant to third-generation cephalosporins have been observed recently in France and the Federal Republic of Germany. This resistance phenotype is due to the production of new plasmid-mediated, broad-substrate-range beta-lactamases designated TEM-3 to TEM-7. DNA-DNA hybridization analysis with a probe specific for TEM-1 indicated that the corresponding genes blaT-3 to blaT-7 were variants of the structural genes for TEM-type beta-lactamases. In the present studies, a 2.5-kilobase BamHI plasmid DNA fragment encoding TEM-3 was cloned in E. coli, and the entire nucleotide sequence of blaT-3 was determined. The deduced amino acid sequence of TEM-3 differed in two positions from that of the TEM-2 enzyme: lysine (TEM-3) was substituted for glutamic acid (TEM-2) at residue 104 and serine (TEM-3) for glycine (TEM-2) at residue 238 in the numbering system of Ambler. Spontaneous mutants of TEM penicillinases with increased activity against third-generation cephalosporins were obtained in vitro by selection on cefotaxime or ceftazidime. It therefore appears that mutations in TEM-type beta-lactamases contribute to resistance to new-generation cephalosporins.
This article was published in Rev Infect Dis and referenced in Journal of Neonatal Biology

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