Reversal of clavulanate resistance conferred by a Ser-244 mutant of TEM-1 β-lactamase as a result of a second mutation (Arg to Ser at position 164) that enhances activity against ceftazidime

U. Imtiaz, E. K. Manavathu, S. Mobashery, S. A. Lerner

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The mutation of Arg-244 to Ser (Arg-244→Ser mutation] in the TEM-1 β- lactamase has been shown to produce resistance to inactivation by clavulanate in the mutant enzyme and resistance to ampicillin plus clavulanate in a strain of Escherichia coli producing this enzyme. The Arg-164→Ser mutation in the TEM-1 β-lactamase (TEM-12 enzyme) is known to enhance the activity of the enzyme against ceftazidime, resulting in resistance to the drug in a strain producing the mutant enzyme (D. A. Weber, C. C. Sanders, J. S. Bakken, and J. P. Quinn, J. Infect. Dis. 162:460-465, 1990). The doubly mutated derivative of the TEM-1 enzyme (Ser-164/Ser-244) retains the characteristics of the Ser-164 mutant enzyme, i.e., enhanced activity against ceftazidime and sensitivity to inactivation by clavulanate. It also confers the same phenotype as the Ser-164 mutant enzyme, i.e., resistance to ceftazidime and ampicillin, with reversal of this resistance in the presence of clavulanate. Thus, the Arg-164→Ser mutation in the TEM-1 β-lactamase suppresses the effect of the Arg-244→Ser mutation which, by itself, reduces the sensitivity of the enzyme to inactivation by clavulanate.

Original languageEnglish (US)
Pages (from-to)1134-1139
Number of pages6
JournalAntimicrobial agents and chemotherapy
Volume38
Issue number5
DOIs
StatePublished - 1994

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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