Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram-Negative Bacteria.
Diane Borselli, Marine Blanchet, Jean-Michel Bolla, Aaron Muth, Kristen Skruber, Otto Phanstiel, Jean Michel Brunel
Author Information
Diane Borselli: Aix-Marseille Université, IRBA, TMCD2 UMR-MD1, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.
Marine Blanchet: 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.
Jean-Michel Bolla: Aix-Marseille Université, IRBA, TMCD2 UMR-MD1, Faculté de Médecine, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.
Aaron Muth: Department of Medical Education, University of Central Florida, 12722 Research Parkway, Orlando, FL, 32826-3227, USA.
Kristen Skruber: Department of Medical Education, University of Central Florida, 12722 Research Parkway, Orlando, FL, 32826-3227, USA.
Otto Phanstiel: Department of Medical Education, University of Central Florida, 12722 Research Parkway, Orlando, FL, 32826-3227, USA.
Jean Michel Brunel: 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.
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.
