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Stages of polymyxin B interaction with the Escherichia coli cell envelope

R Daugelavicius1, E Bakiene, D H Bamford

  • 1Department of Biochemistry and Biophysics, Vilnius University, Ciurlionio 21, LT-2009 Vilnius, Lithuania. daugelav@cc.helsinki.fi

Antimicrobial Agents and Chemotherapy
|October 19, 2000
PubMed

Insights

Polymyxin B increases outer membrane permeability in Escherichia coli at low concentrations, with pore formation and cytoplasmic membrane depolarization occurring only at higher levels. These membrane effects are not essential for polymyxin B's bactericidal action.

Area of Science:

  • Microbiology
  • Membrane Biology
  • Antimicrobial Research

Background:

  • Polymyxin B (PMB) is a crucial antibiotic targeting Gram-negative bacteria.
  • Understanding PMB's membrane interaction mechanism is vital for combating antibiotic resistance.

Purpose of the Study:

  • To investigate the distinct effects of PMB on the outer membrane (OM) and cytoplasmic membrane (CM) permeabilities of Escherichia coli.
  • To elucidate the relationship between PMB-induced membrane alterations and its bactericidal activity.

Main Methods:

  • Monitoring ion and lipophilic compound fluxes across bacterial membranes.
  • Utilizing tetraphenylphosphonium, phenyldicarbaundecaborane, K(+), and H(+) ion flux assays.
  • Examining PMB effects under varying ionic strengths and Mg(2+) concentrations.

Main Results:

  • PMB (2-20 µg/ml) increased OM permeability and caused K(+) leakage without CM depolarization.
  • Higher PMB concentrations induced CM depolarization and formed ion-permeable pores, mimicking bacteriophage channels.
  • PMB's bactericidal effect occurred at sub-lytic concentrations, independent of pore formation and CM depolarization.
  • OM permeabilization was reduced by increased Mg(2+) and affected by ionic strength.

Conclusions:

  • PMB's OM-permeabilizing action is separable from its CM-depolarizing effect.
  • PMB induces ion-permeable pores in the bacterial envelope.
  • Pore formation and CM depolarization are not required for PMB's bactericidal activity or K(+) gradient dissipation.

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