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Intracellular polyamine pools, oligopeptide-binding protein A expression, and resistance to aminoglycosides in

Maria B R Acosta1, Rita C Café Ferreira, Luís C S Ferreira

  • 1Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, 05508-000 São Paulo, SP, Brazil.

Memorias Do Instituto Oswaldo Cruz
|January 18, 2006
PubMed

Insights

Diminished oligopeptide-binding protein (OppA) levels in Escherichia coli increase spermidine, directly impacting kanamycin resistance. This suggests a complex link between OppA, polyamine metabolism, and antibiotic resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Aminoglycoside antibiotics are crucial for treating bacterial infections.
  • Multiple antibiotic resistance is a growing global health concern.
  • Polyamines play vital roles in bacterial physiology and stress response.

Purpose of the Study:

  • To investigate the role of intracellular polyamines (putrescine, spermidine) in multi-drug resistance to aminoglycoside antibiotics.
  • To elucidate the relationship between oligopeptide-binding protein (OppA) levels, ornithine decarboxylase (ODC) activity, and kanamycin resistance in Escherichia coli.

Main Methods:

  • Selection of in vitro kanamycin-resistant Escherichia coli J53 mutants.
  • Analysis of oligopeptide-binding protein (OppA) levels and ornithine decarboxylase (ODC) activity.
  • Quantification of intracellular free polyamine pools (putrescine, spermidine).
  • Treatment with exogenous polyamines and polyamine synthesis inhibitors.

Main Results:

  • Diminished OppA levels, but not defective ODC activity, led to increased relative spermidine concentration.
  • A direct relationship was observed between intracellular OppA levels and kanamycin resistance.
  • Exogenous polyamines and inhibitors modulated antibiotic resistance in mutant strains.

Conclusions:

  • OppA expression is a key factor influencing intracellular spermidine levels and aminoglycoside antibiotic resistance.
  • A complex interplay exists among OppA expression, polyamine metabolism, and aminoglycoside resistance in Escherichia coli.
  • Targeting polyamine metabolism or OppA could offer novel strategies to combat antibiotic resistance.

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