Production of Oligosaccharides as Promising New Food Additive Generation

Nedavna istraživanja ugljikohidratnih sastojaka hrane potvrdila su djelotvornost uporabe oligosaharida kao prebiotika ili biokonzervansa. Prebiotički oligosaharidi imaju različito podrijetlo i strukturu, a biokonzervansi su uglavnom oligohitozani ili hitozani male molekularne mase. Nova biotehnološka proizvodnja bitno je pridonijela razvoju tih funkcionalnih sastojaka hrane, a njihovu primjenu ograničava specifična glikozidna struktura. Ovaj revijalni prikaz donosi niz spoznaja te popis procesa tvorbe bioaktivnih oligosaharida.Recent research in the area of carbohydrate food ingredients has shown the efficiency of oligosaccharides when they are used as prebiotics or biopreservatives. Considering the former, they have various origins and structures, whereas the latter are described mostly as oligochitosans or as low molecular mass chitosans. If new manufacturing biotechnologies have significantly increased the development of these functional food ingredients, the main drawback limiting their applications is the difficulty to engender specific glycosidic structures. The present review focuses on the knowledge in the area of food bioactive oligosaccharides and catalogues the processes employed to generate them

Anthranilic Acid Inhibitors of Undecaprenyl Pyrophosphate Synthase (UppS), an Essential Enzyme for Bacterial Cell Wall Biosynthesis

We report the successful implementation of virtual screening in the discovery of new inhibitors of undecaprenyl pyrophosphate synthase (UppS) from Escherichia coli. UppS is an essential enzyme in the biosynthesis of bacterial cell wall. It catalyzes the condensation of farnesyl pyrophosphate (FPP) with eight consecutive isopentenyl pyrophosphate units (IPP), in which new cis-double bonds are formed, to generate undecaprenyl pyrophosphate. The latter serves as a lipid carrier for peptidoglycan synthesis, thus representing an important target in the antibacterial drug design. A pharmacophore model was designed on a known bisphosphonate BPH-629 and used to prepare an enriched compound library that was further docked into UppS conformational ensemble generated by molecular dynamics experiment. The docking resulted in three anthranilic acid derivatives with promising inhibitory activity against UppS. Compound 2 displayed high inhibitory potency (IC50 = 25 μM) and good antibacterial activity against E. coli BW25113 ΔtolC strain (MIC = 0.5 μg/mL)

In silico identification, synthesis and biological evaluation of novel tetrazole inhibitors of MurB

In the context of antibacterial drug discovery resurgence, novel therapeutic targets and new compounds with alternative mechanisms of action are of paramount importance. We focused on UDP-N- acetylenolpyruvylglucosamine reductase (i.e. MurB), an underexploited target enzyme that is involved in early steps of bacterial peptidoglycan biosynthesis. On the basis of the recently reported crystal structure of MurB in complex with NADP+ , a pharmacopohore model was generated and used in a virtual screening campaign with combined structure-based and ligand-based approaches. In order to explore chemical space around hit compounds, further similarity search and organic synthesis was employed to obtain several compounds with micromolar IC50 values on MurB. The best inhibitors in the reported series of 5-substituted tetrazol-2-yl acetamides were compounds 13, 26 and 30 with IC50 values of 34, 28 and 25 µM, respectively. None of the reported compounds possessed in vitro antimicrobial activity against S. aureus and E. coli

Resilience and development: Mobilizing for transformation

In 2014, the Third International Conference on the resilience of social-ecological systems chose the theme “resilience and development: mobilizing for transformation.” The conference aimed specifically at fostering an encounter between the experiences and thinking focused on the issue of resilience through a social and ecological system perspective, and the experiences focused on the issue of resilience through a development perspective. In this perspectives piece, we reflect on the outcomes of the meeting and document the differences and similarities between the two perspectives as discussed during the conference, and identify bridging questions designed to guide future interactions. After the conference, we read the documents (abstracts, PowerPoints) that were prepared and left in the conference database by the participants (about 600 contributions), and searched the web for associated items, such as videos, blogs, and tweets from the conference participants. All of these documents were assessed through one lens: what do they say about resilience and development? Once the perspectives were established, we examined different themes that were significantly addressed during the conference. Our analysis paves the way for new collective developments on a set of issues: (1) Who declares/assign/cares for the resilience of what, of whom? (2) What are the models of transformations and how do they combine the respective role of agency and structure? (3) What are the combinations of measurement and assessment processes? (4) At what scale should resilience be studied? Social transformations and scientific approaches are coconstructed. For the last decades, development has been conceived as a modernization process supported by scientific rationality and technical expertise. The definition of a new perspective on development goes with a negotiation on a new scientific approach. Resilience is presently at the center of this negotiation on a new science for development. (Résumé d'auteur

L'incidence des infections sur cathéter est-elle modifiée par l'utilisation d'un cathéter à l'argent dans un service de réanimation polyvalente d'un centre hospitalier général?

PARIS-BIUP (751062107) / SudocSudocFranceF

Améliorer la prise en charge médicamenteuse dans un service de gérontologie (recueil et analyse des médicaments non-administrés)

L arrêté du 6 avril 2011 matérialise l engagement d améliorer la qualité de la prise en charge médicamenteuse. Dans ce cadre, un programme d'actions a été élaboré au sein de l hôpital Fernand-Widal. La Délivrance Individuelle Nominative des médicaments (DIN) renforce la sécurisation du circuit des médicaments. Une étude a été mise en place afin de recueillir et analyser les retours de médicaments non-administrés des chariots de DIN des services de soins de suite et de long séjour en gérontologie. L objectif est de les identifier pour garantir le respect de la prescription médicale. Au sein des services de gérontologie, la dispensation des médicaments est réalisée à l aide de chariots composés de tiroirs nominatifs. Après validation pharmaceutique, les médicaments sont dispensés aux services individualisés par patient et par heure d administration. Durant 15 jours, à chaque retour de chariot, nous avons comptabilisé les médicaments non administrés dans les tiroirs des patients. Chaque retour de médicament a été comparé avec la prescription initiale. Les médicaments ont été catégorisés en fonction de leur classe pharmacologique et de leur caractère conditionnel ou non. Les causes principales de non-administrations ont été identifiées. Une analyse des discordances a été réalisée entre le ressenti des médecins sur ce qui est réellement administré ou non. Enfin, une enquête sur le degré de gravité de la non-administration des médicaments a été menée auprès des médecins, pharmaciens et infirmiers. Ces résultats ont permis de mettre en place des actions afin d optimiser la prise en charge du patient. Cette étude s inscrit dans une dynamique d amélioration du processus qualité.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Anthranilic acid inhibitors of undecaprenyl pyrophosphate synthase (UppS), an essential enzyme for bacterial cell wall biosynthesis

We report the successful implementation of virtual screening in the discovery of new inhibitors of undecaprenyl pyrophosphate synthase (UppS) from Escherichia coli. UppS is an essential enzyme in the biosynthesis of bacterial cell wall. It catalyzes the condensation of farnesyl pyrophosphate (FPP) with eight consecutive isopentenyl pyrophosphate units (IPP), in which new cis-double bonds are formed, to generate undecaprenyl pyrophosphate. The latter serves as a lipid carrier for peptidoglycan synthesis, thus representing an important target in the antibacterial drug design. A pharmacophore model was designed on a known bisphosphonate BPH-629 and used to prepare an enriched compound library that was further docked into UppS conformational ensemble generated by molecular dynamics experiment. The docking resulted in three anthranilic acid derivatives with promising inhibitory activity against UppS. Compound 2 displayed high inhibitory potency (IC50 = 25 μM) and good antibacterial activity against E. coli BW25113 ΔtolC strain (MIC = 0.5 μ/mL)

The Biology of Colicin M and Its Orthologs

The misuse of antibiotics during the last decades led to the emergence of multidrug resistant pathogenic bacteria. This phenomenon constitutes a major public health issue. Consequently, the discovery of new antibacterials in the short term is crucial. Colicins, due to their antibacterial properties, thus constitute good candidates. These toxin proteins, produced by E. coli to kill enteric relative competitors, exhibit cytotoxicity through ionophoric activity or essential macromolecule degradation. Among the 25 colicin types known to date, colicin M (ColM) is the only one colicin interfering with peptidoglycan biosynthesis. Accordingly, ColM develops its lethal activity in E. coli periplasm by hydrolyzing the last peptidoglycan precursor, lipid II, into two dead-end products, thereby leading to cell lysis. Since the discovery of its unusual mode of action, several ColM orthologs have also been identified based on sequence alignments; all of the characterized ColM-like proteins display the same enzymatic activity of lipid II degradation and narrow antibacterial spectra. This publication aims at being an exhaustive review of the current knowledge on this new family of antibacterial enzymes as well as on their potential use as food preservatives or therapeutic agents

CbrA mediates colicin M resistance in Escherichia coli through modification of undecaprenyl-phosphate-linked peptidoglycan precursors

Publisher: American Society for Microbiology Journals Section: Research ArticleInternational audienceColicin M is an enzymatic bacteriocin produced by some Escherichia coli strains which provokes cell lysis of competitor strains by hydrolysis of the cell-wall peptidoglycan lipid II precursor. The overexpression of a gene, cbrA (yidS), was shown to protect E. coli cells from the deleterious effects of this colicin but the underlying resistance mechanism was not established. We here report that a major structural modification of the undecaprenyl-phosphate carrier lipid and of its derivatives occurred in membranes of CbrA-overexpressing cells, which explains the acquisition of resistance towards this bacteriocin. Indeed, a main fraction of these lipids, including the lipid II peptidoglycan precursor, now display a saturated isoprene unit at the α-position, i.e. the unit closest to the colicin M cleavage site. Only unsaturated forms of these lipids were normally detectable in wild-type cells. In vitro and in vivo assays showed that colicin M did not hydrolyze α-saturated lipid II, clearly identifying this substrate modification as the resistance mechanism. These saturated forms of undecaprenyl-phosphate and lipid II remained substrates of the different enzymes participating in peptidoglycan biosynthesis and carrier lipid recycling, allowing this colicin M-resistance mechanism to occur without affecting this essential pathway. IMPORTANCE Overexpression of the chromosomal cbrA gene allows E. coli to resist to colicin M (ColM), a bacteriocin specifically hydrolyzing the lipid II peptidoglycan precursor of targeted cells. This resistance results from a CbrA-dependent modification of the precursor structure, i.e. reduction of the α-isoprenyl bond of C55-carrier lipid moiety that is proximal to ColM cleavage site. This modification, observed here for the first time in eubacteria, annihilates the ColM activity without affecting peptidoglycan biogenesis. These data, which further increase our knowledge on the substrate specificity of this colicin, highlight the capability of E. coli to generate reduced forms of C55-carrier lipid and its derivatives. Whether the function of this modification is only relevant with respect to ColM resistance is now questioned