title: Do physiological roles foster persistence of drug/multidrug-efflux transporters? A case study.
abstract: Drug and multidrug resistance have greatly compromised the compounds that were once the mainstays of antibiotic therapy. This resistance often persists despite reductions in the use of antibiotics, indicating that the proteins encoded by antibiotic-resistance genes have alternative physiological roles that can foster such persistence in the absence of selective pressure by antibiotics. The recent observations that Tet(L), a tetracycline-efflux transporter, and MdfA, a multidrug-efflux transporter, both confer alkali tolerance offer a striking case study in support of this hypothesis.
authors.affiliation: Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Terry A
authors.initials: TA
authors.lastname: Krulwich
authors.forename: Oded
authors.initials: O
authors.lastname: Lewinson
authors.forename: Etana
authors.initials: E
authors.lastname: Padan
authors.forename: Eitan
authors.initials: E
authors.lastname: Bibi
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017920:Antiporters / Q000502:physiology; D001419:Bacteria / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D026901:Membrane Transport Proteins / Q000502:physiology; D027961:Potassium-Hydrogen Antiporters / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D013752:Tetracycline / Q000494:pharmacology; D013753:Tetracycline Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D017920:Antiporters; D029968:Escherichia coli Proteins; C118438:Mdfa protein, E coli; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027961:Potassium-Hydrogen Antiporters; D017923:Sodium-Hydrogen Exchangers; C424711:Tet(L) protein, E coli; D013752:Tetracycline