Intervening with Urinary Tract Infections Using Anti-Adhesives Based on the Crystal Structure of the FimH–Oligomannose-3 Complex

Escherichia coli strains adhere to the normally sterile human uroepithelium using type 1 pili, that are long, hairy surface organelles exposing a mannose-binding FimH adhesin at the tip. A small percentage of adhered bacteria can successfully invade bladder cells, presumably via pathways mediated by the high-mannosylated uroplakin-Ia and alpha3beta1 integrins found throughout the uroepithelium. Invaded bacteria replicate and mature into dense, biofilm-like inclusions in preparation of fluxing and of infection of neighbouring cells, being the major cause of the troublesome recurrent urinary tract infections.We demonstrate that alpha-D-mannose based inhibitors of FimH not only block bacterial adhesion on uroepithelial cells but also antagonize invasion and biofilm formation. Heptyl alpha-D-mannose prevents binding of type 1-piliated E. coli to the human bladder cell line 5637 and reduces both adhesion and invasion of the UTI89 cystitis isolate instilled in mouse bladder via catheterization. Heptyl alpha-D-mannose also specifically inhibited biofilm formation at micromolar concentrations. The structural basis of the great inhibitory potential of alkyl and aryl alpha-D-mannosides was elucidated in the crystal structure of the FimH receptor-binding domain in complex with oligomannose-3. FimH interacts with Man alpha1,3Man beta1,4GlcNAc beta1,4GlcNAc in an extended binding site. The interactions along the alpha1,3 glycosidic bond and the first beta1,4 linkage to the chitobiose unit are conserved with those of FimH with butyl alpha-D-mannose. The strong stacking of the central mannose with the aromatic ring of Tyr48 is congruent with the high affinity found for synthetic inhibitors in which this mannose is substituted for by an aromatic group.The potential of ligand-based design of antagonists of urinary tract infections is ruled by the structural mimicry of natural epitopes and extends into blocking of bacterial invasion, intracellular growth and capacity to fluxing and of recurrence of the infection

Modelling approach for the rainfall erosivity index in sub-humid urban areas in northern Algeria

This work presents an approach for storm water erosivity index modelling in the absence of measurement in an urban area, in a sub-humid climate. In torrential storms, floods, loaded with sediments, obstruct storm water drainage. With the aim of estimating the amount of sediment that can be deposited on a stretch of road, adjacent to the study area, the erosivity index is determined from a count of 744 rain showers recorded over a period of 19 years. The Universal Soil Loss Equation (USLE) of Wischmeier and Smith is applied, where only the index of erosivity is calculated; it is based on the intensity of the rain starting the process of erosion in the basin. Functional relations are required between this factor and the explanatory variables. A power type regression model is reached, making it possible to bring a decision-making aid in absences of measurements

MEDFRIEND : global perspectives for the UNESCO research network in hydrology for the Mediterranean

MEDFRIEND est l'un des huit programmes FRIEND du Programme hydrologique international de l'Unesco. Son but est de promouvoir la recherche collaborative entre pays voisins en hydrologie et sciences associées, dans plusieurs thèmes de recherche majeurs pour la région. Ces thèmes sont : érosion et transport solide, écohydrologie côtière, hydrogéologie karstique, événements extrêmes, impact du changement global sur les régimes hydrologiques et ressources en eau. Une base de données commune a été élaborée et est accessible aux membres uniquement. Le programme MEDFRIEND a démarré en janvier 2009, suivant le programme FRIEND-AMHY qui avait débuté en 1991. Il y a pour le moment 17 pays riverains de la Méditerranée dans MEDFRIEND. Les types d'activités coordonnées par MEDFRIEND sont les suivants : ateliers scientifiques, conférences internationales, formations de groupe, échanges scientifiques. (Résumé d'auteur

Chemical Composition of the Volatile Components of Tropaeolum majus L. (Garden Nasturtium) from North Western Algeria

Essential oil from Tropaeolum majus L. aerial parts, a plant native to North Western Algeria, was obtained by hydrodistillation. The oil volatile components were identified by a combination of gas chromatography/flame ionization detection (GC/FID), GC-mass spectrometry (GC-MS) techniques, and NMR spectroscopy. Nine components representing 92.0 % of the essential oil total (GC/FID chromatogram) were identified. The most abundant compounds were benzyl isothiocyanate (82.5 %), benzene acetonitrile (3.9 %) and 2-phenylethyl isovalerate (2.9 %). Higher content in nitrogen- and sulfur-containing compounds accounting to 86.4 % of the volatile fraction composition of T. majus were quantified

Templating Gold Surfaces with Function: A Self-Assembled Dendritic Monolayer Methodology Based on Monodisperse Polyester Scaffolds

The antibiotic resistance developed among several pathogenic bacterial strains has spurred interest in understanding bacterial adhesion down to a molecular level. Consequently, analytical methods that rely on bioactive and multivalent sensor surfaces are sought to detect and suppress infections. To deliver functional sensor surfaces with an optimized degree of molecular packaging, we explore a library of compact and monodisperse dendritic scaffolds based on the nontoxic 2,2-bis(methylol)propionic acid (bis-MPA). A self-assembled dendritic monolayer (SADM) methodology to gold surfaces capitalizes on the design of aqueous soluble dendritic structures that bear sulfur-containing core functionalities. The nature of sulfur (either disulfide or thiol), the size of the dendritic framework (generation 1–3), the distance between the sulfur and the dendritic wedge (4 or 14 Å), and the type of functional end group (hydroxyl or mannose) were key structural elements that were identified to affect the packaging densities assembled on the surfaces. Both surface plasmon resonance (SPR) and resonance-enhanced surface impedance (RESI) experiments revealed rapid formation of homogenously covered SADMs on gold surfaces. The array of dendritic structures enabled the fabrication of functional gold surfaces displaying molecular covering densities of 0.33–2.2 molecules·nm–2 and functional availability of 0.95–5.5 groups·nm–2. The cell scavenging ability of these sensor surfaces for Escherichia coli MS7fim+ bacteria revealed 2.5 times enhanced recognition for G3-mannosylated surfaces when compared to G3-hydroxylated SADM surfaces. This promising methodology delivers functional gold sensor surfaces and represents a facile route for probing surface interactions between multivalently presented motifs and cells in a controlled surface setting