title: Synthetic hydraphile channels of appropriate length kill Escherichia coli.
abstract: Crown ether-based synthetic cation conducting channels called hydraphiles show clear ionophoretic activity in phospholipid vesicles. These compounds are shown to be active against the bacterium E. coli. Disk diffusion assays were performed to assess the toxicity of different hydraphile derivatives. Liquid culture tests were conducted to quantitate the dependence of bacterical activity on channel length. It is proposed that hydraphiles are toxic to bacteria as a result of channel formation in the membrane. The bactericidal activity is found to depend at least on the presence of a functional central relay and proper channel length. It is speculated that hydraphiles insert into the bilayer and disrupt the cell's osmotic balance, leading to cell death.
authors.affiliation: Bioorganic Chemistry Program, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8103, St. Louis, Missouri 63110, USA.
authors.forename: W Matthew
authors.initials: WM
authors.lastname: Leevy
authors.forename: Gina M
authors.initials: GM
authors.lastname: Donato
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ferdani
authors.forename: William E
authors.initials: WE
authors.lastname: Goldman
authors.forename: Paul H
authors.initials: PH
authors.lastname: Schlesinger
authors.forename: George W
authors.initials: GW
authors.lastname: Gokel
mesh_terms: D000668:Ampicillin Resistance; D004926:Escherichia coli / Q000187:drug effects*; D007202:Indicators and Reagents; D007473:Ion Channels / Q000737:chemistry / Q000494:pharmacology*; D007478:Iontophoresis; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D010743:Phospholipids; D012964:Sodium / Q000378:metabolism
chemical_list: D007202:Indicators and Reagents; D007473:Ion Channels; D008051:Lipid Bilayers; D010743:Phospholipids; D012964:Sodium