Antibiotic uptake through membrane channels: role of Providencia stuartii OmpPst1 porin in carbapenem resistance

Biochemistry. 2012 Dec 21;51(51):10244-9. doi: 10.1021/bi301398j. Epub 2012 Dec 11.

Abstract

The role of major porin OmpPst1 of Providencia stuartii in antibiotic susceptibility for two carbapenems is investigated by combining high-resolution conductance measurements, liposome swelling, and microbiological assays. Reconstitution of a single OmpPst1 into a planar lipid bilayer and measuring the ion current, in the presence of imipenem, revealed a concentration-dependent decrease in conductance, whereas meropenem produced well-resolved short ion current blockages. Liposome swelling assays suggested a small flux of imipenem in contrast to a rapid permeation of meropenem. The lower antibiotic susceptibility of P. stuartii to imipenem compared to meropenem correlated well with the decreased level of permeation of the former through the OmpPst1 channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / metabolism
  • Cell Membrane / metabolism
  • Drug Resistance, Bacterial / physiology
  • Electric Conductivity
  • Imipenem / metabolism*
  • Lipid Bilayers / metabolism
  • Liposomes / metabolism
  • Meropenem
  • Microbial Sensitivity Tests
  • Porins / metabolism*
  • Providencia / drug effects*
  • Providencia / metabolism
  • Thienamycins / metabolism*

Substances

  • Bacterial Outer Membrane Proteins
  • Lipid Bilayers
  • Liposomes
  • Porins
  • Thienamycins
  • Imipenem
  • Meropenem