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 Citations (Scopus)

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 - Jan 1 1994

Fingerprint

Clavulanic Acid
Ceftazidime
Mutation
Enzymes
Ampicillin Resistance
Ampicillin
Drug Resistance
Escherichia coli
Phenotype

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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

In: Antimicrobial Agents and Chemotherapy, Vol. 38, No. 5, 01.01.1994, p. 1134-1139.

Research output: Contribution to journalArticle

@article{8b1508cc8bbc4e7889960cd13cc7c922,
title = "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",
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.",
author = "U. Imtiaz and Manavathu, {E. K.} and S. Mobashery and Lerner, {S. A.}",
year = "1994",
month = "1",
day = "1",
doi = "10.1128/AAC.38.5.1134",
language = "English (US)",
volume = "38",
pages = "1134--1139",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "5",

}

TY - JOUR

T1 - 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

AU - Imtiaz, U.

AU - Manavathu, E. K.

AU - Mobashery, S.

AU - Lerner, S. A.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0028222371&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028222371&partnerID=8YFLogxK

U2 - 10.1128/AAC.38.5.1134

DO - 10.1128/AAC.38.5.1134

M3 - Article

C2 - 8067751

AN - SCOPUS:0028222371

VL - 38

SP - 1134

EP - 1139

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 5

ER -