title: Antibiotic uptake through membrane channels: role of Providencia stuartii OmpPst1 porin in carbapenem resistance.
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.
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Bremen, Germany.
authors.forename: Harsha
authors.initials: H
authors.lastname: Bajaj
authors.forename: Que-Tien
authors.initials: QT
authors.lastname: Tran
authors.forename: Kozhinjampara R
authors.initials: KR
authors.lastname: Mahendran
authors.forename: Chady
authors.initials: C
authors.lastname: Nasrallah
authors.forename: Jacques-Phillippe
authors.initials: JP
authors.lastname: Colletier
authors.forename: Anne
authors.initials: A
authors.lastname: Davin-Regli
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bolla
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Pagès
authors.forename: Mathias
authors.initials: M
authors.lastname: Winterhalter
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000502:physiology; D004553:Electric Conductivity; D015378:Imipenem / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000378:metabolism*; D011532:Providencia / Q000187:drug effects* / Q000378:metabolism; D013845:Thienamycins / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D018272:Porins; D013845:Thienamycins; D015378:Imipenem; D000077731:Meropenem