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Squalamine, a new antibiotic extracted from marine environment

Abstract number: P1126

Alhanout K.

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 [1] 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. [1]

Squalamine

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 [2] of a structural analogue of squalamine [2] 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. [3] 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.

References

1. Brunel, J.M.; Salmi, C.; Loncle, C.; Vidal, N.; Letourneux, Y. Curr Cancer Drug Targets 2005, 5, 267–272.

2. Loncle, C., Salmi, C., Letourneux, Y., Brunel, J. M. Tetrahedron 2007, 63, 12968–2974.

3. Salmi, C.; Loncle, C.; Vidal, N.; Letourneux, Y.; Fantini, J.; Maresca, M.; Taïeb, N.; Pagès, J. M.; Brunel, J. M. Plos One 2008, 3(7), e2765.

Session Details

Date: 16/05/2009
Time: 00:00-00:00
Session name: 19th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Helsinki, Finland, 16 - 19 May 2009
Presentation type:
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