title: Hydraphiles enhance antimicrobial potency against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis.
abstract: Hydraphiles are synthetic amphiphiles that form ion-conducting pores in liposomal membranes. These pores exhibit open-close behavior when studied by planar bilayer conductance techniques. In previous work, we showed that when co-administered with various antibiotics to the DH5α strain of Escherichia coli, they enhanced the drug's potency. We report here potency enhancements at low concentrations of hydraphiles for the structurally and mechanistically unrelated antibiotics erythromycin, kanamycin, rifampicin, and tetracycline against Gram negative E. coli (DH5α and K-12) and Pseudomonas aeruginosa, as well as Gram positive Bacillus subtilis. Earlier work suggested that potency increases correlated to ion transport function. The data presented here comport with the function of hydraphiles to enhance membrane permeability in addition to, or instead of, their known function as ion conductors.
authors.affiliation: Center for Nanoscience, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA; Department of Biology, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA.
authors.forename: Mohit B
authors.initials: MB
authors.lastname: Patel
authors.affiliation: Department of Biology, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA.
authors.forename: Evan C
authors.initials: EC
authors.lastname: Garrad
authors.affiliation: Department of Biology, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Stavri
authors.affiliation: Upaya Pharmaceuticals, LLC, 4633 World Pkwy. Cir., Berkeley, MO 63134, USA; Center for Nanoscience, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gokel
authors.affiliation: Center for Nanoscience, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA; Department of Chemistry & Biochemistry, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA.
authors.forename: Saeedeh
authors.initials: S
authors.lastname: Negin
authors.affiliation: Center for Nanoscience, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA; Department of Chemistry & Biochemistry, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Meisel
authors.affiliation: Department of Cell Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Cusumano
authors.affiliation: Center for Nanoscience, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA; Department of Chemistry & Biochemistry, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA; Department of Biology, University of Missouri-St. Louis, 1 University Blvd., St. Louis, MO 63121, USA; Upaya Pharmaceuticals, LLC, 4633 World Pkwy. Cir., Berkeley, MO 63134, USA. Electronic address: gokelg@umsl.edu.
authors.forename: George W
authors.initials: GW
authors.lastname: Gokel
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000378:metabolism; D004917:Erythromycin / Q000493:pharmacokinetics / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000188:drug therapy; D006801:Humans; D007612:Kanamycin / Q000493:pharmacokinetics / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010539:Permeability / Q000187:drug effects*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D012293:Rifampin / Q000493:pharmacokinetics / Q000494:pharmacology; D013501:Surface-Active Agents / Q000737:chemistry* / Q000494:pharmacology*; D013752:Tetracycline / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013501:Surface-Active Agents; D007612:Kanamycin; D004917:Erythromycin; D013752:Tetracycline; D012293:Rifampin
keywords: Antimicrobials; B. subtilis; Crown ethers; E. coli; Erythromycin; Hydraphiles; Kanamycin; Membrane permeability; P. aeruginosa; Rifampicin; Synthetic ion channels; Tetracycline