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Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
09:00

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance

Published on: May 2, 2018

Leucine and serine induce mecillinam resistance in Escherichia coli

P Bouloc1, D Vinella, R D'Ari

  • 1Institut Jacques Monod, CNRS, Université Paris, France.

Molecular & General Genetics : MGG
|November 1, 1992
PubMed

Insights

Escherichia coli becomes resistant to mecillinam when starved of isoleucine and valine. This resistance is linked to the stringent response, a cellular stress mechanism, and can be reversed by adding these amino acids.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • The stringent response, mediated by RelA and characterized by a high guanosine tetraphosphate (ppGpp) pool, is known to induce resistance to the beta-lactam antibiotic mecillinam in Escherichia coli.
  • This phenomenon is typically observed under conditions of partial amino acid starvation.

Purpose of the Study:

  • To investigate the specific amino acid requirements for mecillinam resistance in Escherichia coli.
  • To elucidate the role of the stringent response in mediating this resistance.

Main Methods:

  • Testing mecillinam sensitivity of wild-type Escherichia coli in the presence of various amino acids (L-leucine, L-serine, L-cysteine, L-isoleucine, L-valine).
  • Assessing the RelA-dependence of mecillinam resistance induced by L-serine.
  • Evaluating the effect of amino acid supplementation on established resistance.

Main Results:

  • Wild-type Escherichia coli, sensitive to mecillinam on minimal glucose, exhibits resistance when supplemented with L-leucine or L-serine.
  • This resistance is specific to mecillinam and is reversed by the addition of L-isoleucine and L-valine.
  • The resistance induced by L-serine is dependent on the RelA protein, indicating RelA-mediated stringent response activation.

Conclusions:

  • Supplementation of growth media with L-leucine or L-serine induces partial starvation for L-isoleucine/L-valine in Escherichia coli.
  • This induced amino acid imbalance triggers the stringent response, leading to mecillinam resistance.
  • The findings highlight a specific nutritional trigger for the stringent response and its direct impact on antibiotic resistance in E. coli.

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