Squalamine: An Appropriate Strategy against the Emergence of Multidrug Resistant Gram-Negative Bacteria?

We reported that squalamine is a membrane-active molecule that targets the membrane integrity as demonstrated by the ATP release and dye entry. In this context, its activity may depend on the membrane lipid composition. This molecule shows a preserved activity against bacterial pathogens presenting a noticeable multi-resistance phenotype against antibiotics such as polymyxin B. In this context and because of its structure, action and its relative insensitivity to efflux resistance mechanisms, we have demonstrated that squalamine appears as an alternate way to combat MDR pathogens and by pass the gap regarding the failure of new active antibacterial molecules

Synthèse de nouveaux dérivés aminostéroïdes et phospholipides à potentialité thérapeutique et de nouvelles prodrogues lipidiques d'inhibiteurs d'enzymes

LA ROCHELLE-BU (173002101) / SudocSudocFranceF

Les mollusques du genre Conus et les applications thérapeutiques de leurs venins

Les mollusques gastéropodes du genre Conus sont des prédateurs marins caractérisés par un appareil venimeux très perfectionné et des techniques de chasses remarquables. Ils peuvent être à l'origine d'envenimations graves voire mortelles chez l'homme. Les toxines contenues dans le venin des cônes, nommées conotoxines, agissent en synergie afin de paralyser les proies. Elles perturbent le fonctionnement du système nerveux et des muscles. La spécificité d'action physiologique des conotoxines en fait d'excellents candidats pour l'élaboration de nouveaux médicaments.NANTES-BU Médecine pharmacie (441092101) / SudocSudocFranceF

A comparison of three rapid and accurate bioluminescent antibiotic susceptibility tests

International audienceIntroduction: Rapid determination of microorganisms' antibiotic susceptibility remains a great challenge for the clinical diagnosis of infectious diseases. In this study, we compare three rapid bioluminescent antibiotic susceptibility tests with the conventional normalised microdilution method. Methods: The susceptibility of two bacterial and two fungal strains to a 6 h incubation with one of eight standard antibiotics was investigated by the ATP, AK and QNO bioluminescent methods. Results: Three rapid and accurate antibiotic susceptibility testing were investigated performing ATP, AK and QNO bioluminescent assays. All the results were in accordance with those obtained using a standard microdilution assay. All these methods were sensitive and faster than the previously well-known ones. Discussion: The development of bioluminescent determination methods could lead to accurate and useful antibiotic susceptibility testing. (C) 2009 Elsevier Inc. All rights reserved

Biodiversity of the genus Conus (Fleming, 1822): a rich source of bioactive peptides

International audienceIn this paper, we present an overview of the biodiversity of both marine snails of the large genus Conus and their venoms. After a brief survey of Conidae malacology, we focus on the high degree of biodiversity of this genus, its specific biogeography as well as its habitat, and the relatively strict diet of its members. The venom of Conidae species contains a large number of peptides that can interact selectively with key elements of the peripheral and central nervous systems of vertebrates and invertebrates. Emphasis is on summarizing our current knowledge of the specific actions of venom components on ionic channels, receptors and other key elements of cellular communication. The peptides isolated from venoms, called conotoxins, form different families according to both their primary structure and their specific pharmacological targets. Three families encompassing the mu-, muO- and delta-conotoxins target voltage-sensitive sodium channels but with different modes of action or tissue selectivity. Another important class of conotoxins is the omega-conotoxin family which acts on voltage-sensitive calcium channels. The alpha-conotoxin family is represented by several peptides blocking muscular or neuronal nicotinic acetylcholine receptors. Finally, a blocker of potassium channels is presented as well as two conotoxins acting on the N-Methyl-D-Aspartate receptor. Primary structures and cysteine frameworks of all these conotoxins are shown and compared. At the end of the review, we report the contribution of molecular biology to identification of new conotoxins having original pharmacological properties. In conclusion, conotoxins have received increasing attention from physiologists, pharmacologists, biochemists and physicians because of their selectivity as well as their pharmacological and therapeutic potential