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

Rev Infect Dis. 1988 Jul-Aug;10(4):879-84. doi: 10.1093/clinids/10.4.879.

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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cephalosporins / pharmacology*
  • Citrobacter / drug effects
  • Citrobacter / enzymology
  • Citrobacter / genetics*
  • Cloning, Molecular
  • DNA, Bacterial / genetics
  • Drug Resistance, Microbial / genetics
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / enzymology
  • Klebsiella pneumoniae / genetics*
  • Mutation
  • Nucleic Acid Hybridization
  • Penicillinase / genetics*
  • R Factors
  • Sequence Homology, Nucleic Acid
  • Transformation, Bacterial

Substances

  • Cephalosporins
  • DNA, Bacterial
  • Penicillinase