Squalamine, a new antibiotic extracted from marine environment
Abstract number: P1126
Objectives: Extensive use of antibiotics has raised a serious public health problem due to infections caused by multidrug-resistant bacterial pathogens. Consequently, there is a pressing need to develop new antibiotics to keep pace with bacterial resistance. Recently, a new aminosterol called squalamine  has been isolated from tissues of the dogfish shark, Squalus acanthias. This unusual natural product has attracted considerable interest because of its potent antimicrobial activities against a broad spectrum of microorganisms. 
Methods: The feasibility of obtaining large quantities of this steroidal antibiotic, from natural sources or by synthesis, appears questionable. In order to understand the structure-activity relatationships of such compounds, we have recently developed the synthesis  of a structural analogue of squalamine  mimicking not only its structure but also its antimicrobial properties.
Results: We have envisioned the possibility that these derivatives might be able to disrupt the organisation of the Gram-negative bacterial membranes. The antibacterial action manifested via permeabilisation of the outer membrane of Escherichia coli bacteria has been demonstrated.  On the other hand, a different mechanism of action of such derivatives towards Gram-positive bacteria has been determined by electron microscopy analysis and membrane depolarisation measurements and will be discussed.
Conclusion: Squalamine is a membrane-active molecule that targets the membrane integrity and consequently, its activity and mechanism of action corelates with the membrane lipid composition.
|Session name:||19th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Helsinki, Finland, 16 - 19 May 2009|
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