title: The Escherichia coli multidrug transporter MdfA catalyzes both electrogenic and electroneutral transport reactions.
abstract: The resistance of cells to many drugs simultaneously (multidrug resistance) often involves the expression of membrane transporters (Mdrs); each recognizes and expels a broad spectrum of chemically unrelated drugs from the cell. The Escherichia coli Mdr transporter MdfA is able to transport differentially charged substrates in exchange for protons. This includes neutral compounds, namely chloramphenicol and thiamphenicol, and lipophilic cations such as tetraphenylphosphonium and ethidium. Here we show that the chloramphenicol and thiamphenicol transport reactions are electrogenic, whereas the transport of several monovalent cationic substrates is electroneutral. Therefore, unlike with positively charged substrates, the transmembrane electrical potential (negative inside) constitutes a major part of the driving force for the transport of electroneutral substrates by MdfA. These results demonstrate an unprecedented ability of a single secondary transporter to catalyze discrete transport reactions that differ in their electrogenicity and are governed by different components of the proton motive force.
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Lewinson
authors.forename: Julia
authors.initials: J
authors.lastname: Adler
authors.forename: Gerrit J
authors.initials: GJ
authors.lastname: Poelarends
authors.forename: Piotr
authors.initials: P
authors.lastname: Mazurkiewicz
authors.forename: Arnold J M
authors.initials: AJ
authors.lastname: Driessen
authors.forename: Eitan
authors.initials: E
authors.lastname: Bibi
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001692:Biological Transport; D002384:Catalysis; D002701:Chloramphenicol / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D006863:Hydrogen-Ion Concentration; D026901:Membrane Transport Proteins / Q000378:metabolism*; D011510:Proteolipids
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C118438:Mdfa protein, E coli; D026901:Membrane Transport Proteins; D011510:Proteolipids; C020485:proteoliposomes; D002701:Chloramphenicol