Motuporamine Derivatives as Antimicrobial Agents and Antibiotic Enhancers against Resistant Gram-Negative Bacteria
- Diane Borsellic(Author),
- Marine Blanchetc(Author),
- Jean Michel Bollac(Author),
- Aaron Mutha(Author),
- ,
- Otto Phanstiela(Author)
- aUniversity of Central Florida,
- bDepartment of Medical Education,
- cAix–Marseille Université
Research Output: Contribution to journal Article Peer-review
Open access
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.