title: Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram-Negative Bacteria.
abstract: Dihydromotuporamine C and its derivatives were evaluated for their in vitro antimicrobial activities and antibiotic enhancement properties against Gram-negative bacteria and clinical isolates. The mechanism of action of one of these derivatives, MOTU-N44, was investigated against Enterobacter aerogenes by using fluorescent dyes to evaluate outer-membrane depolarization and permeabilization. Its efficiency correlated with inhibition of dye transport, thus suggesting that these molecules inhibit drug transporters by de-energization of the efflux pump rather than by direct interaction of the molecule with the pump. This suggests that depowering the efflux pump provides another strategy to address antibiotic resistance.
authors.affiliation: Aix-Marseille Université, IRBA, TMCD2 UMR-MD1, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Borselli
authors.affiliation: Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS, UMR7258, Institut Paoli Calmettes, Aix-Marseille Université, UM 105, Inserm, U1068, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Blanchet
authors.affiliation: Aix-Marseille Université, IRBA, TMCD2 UMR-MD1, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bolla
authors.affiliation: Department of Medical Education, University of Central Florida, 12722 Research Parkway, Orlando, FL, 32826-3227, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Muth
authors.affiliation: Department of Medical Education, University of Central Florida, 12722 Research Parkway, Orlando, FL, 32826-3227, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Skruber
authors.affiliation: Department of Medical Education, University of Central Florida, 12722 Research Parkway, Orlando, FL, 32826-3227, USA.
authors.forename: Otto
authors.initials: O
authors.lastname: Phanstiel
authors.affiliation: Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS, UMR7258, Institut Paoli Calmettes, Aix-Marseille Université, UM 105, Inserm, U1068, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Brunel
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D021902:Enterobacter aerogenes / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000494:pharmacology*; D026901:Membrane Transport Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D006573:Heterocyclic Compounds, 1-Ring; C000618845:MOTU-N44 compound; D026901:Membrane Transport Proteins; D011073:Polyamines; C409087:motuporamine A
keywords: antibiotics; antimicrobial agents; bacterial resistance; membranes; motuporamine; polyamine derivatives