Staphylocoque doré | EPFL Graph Search

Le staphylocoque doré (Staphylococcus aureus) est l'espèce la plus pathogène du genre Staphylococcus. Elle est responsable d'intoxications alimentaires, d'infections localisées suppurées et, dans certains cas extrêmes, d'infections potentiellement mortelles (patient immunodéprimé, prothèses cardiaques). S. aureus se présente comme une coque en amas (grappes de raisin), Gram positif et catalase positif. Sa teneur en caroténoïdes lui confère une couleur dorée à l'origine de son nom. Écologie Habitat L'espèce S. aureus est commensale de l'homme (elle est présente chez 15 à 30 % des individus dits porteurs sains chez qui elle a un rôle de protection écologique) et se révèle pathogène opportuniste dans certains emplacements ou dans certaines circonstances. C'est un germe :

ubiquitaire : S. aureus possède une bonne résistance aux mécanismes d'épuration naturels (oxydation, dessiccation, ce qui explique sa transmission directe mais aussi indirecte) ;
commensal : S

Solar photo-Fenton disinfection of 11 antibiotic-resistant bacteria (ARB) and elimination of representative AR genes. Evidence that antibiotic resistance does not imply resistance to oxidative treatment

Stefanos Giannakis, Truong-Thien Melvin Le, César Pulgarin

The emergence of antibiotic resistance represents a major threat to human health. In this work we investigated the elimination of antibiotic resistant bacteria (ARB) by solar light and solar photo-Fenton processes. As such, we have designed an experimental plan in which several bacterial strains (Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae) possessing different drug-susceptible and -resistant patterns and structures (Gram-positive and Gram-negative) were subjected to solar light and the photo-Fenton oxidative treatment in water. We showed that both solar light and solar photo-Fenton processes were effective in the elimination of ARB in water and that the time necessary for solar light disinfection and solar photo-Fenton disinfection were similar for antibiotic-susceptible and antibiotic-resistant strains (mostly 180-240 and 90-120 min, respectively). Moreover, the bacterial structure did not significantly affect the effectiveness of the treatment. Similar regrowth pattern was observed (compared to the susceptible strain) and no development of bacteria with higher drug-resistance values was found in waters after any treatment. Finally, both processes were effective to reduce AR genes (ARGs), although solar photo-Fenton was more rapid than solar light. In conclusion, the solar photo-Fenton process ensured effective disinfection of ARB and elimination of ARGs in water (or wastewater) and is a potential mean to ensure limitation of ARB and ARG spread in nature. (C) 2018 Elsevier Ltd. All rights reserved.

PERGAMON-ELSEVIER SCIENCE LTD2018

Metal nanoparticles functionalized carbon nanotubes for efficient catalytic application

Lakshmi Devi Chakkarapani

Surfactant molecules were non-covalently functionalized with carbon nanotubes (CNTs) to retain the remarkable properties of CNTs. Moreover, silver nanoparticles (AgNPs) were immobilized onto CNTs-surfactant matrixes to enhance the catalytic and biomedical utility of carbon nanotubes. The structure and morphology of the newly prepared nanohybrids were investigated by spectroscopic and microscopic analyses. The catalytic efficiency of the nanohybrids was examined for Trypan blue reduction as a model reaction and the observed rate constant was calculated as 14.05 x 10(-2) min(-1). The antimicrobial activities of the nanohybrids were studied against two representative bacterial pathogens, such as Pseudomonas aeruginosa and Staphylococcus aureus. The highest zone of inhibition for those bacterial pathogens was found as 26 and 33 mm.

2019

Improving Bicyclic Peptide Phage Display and Development of Sortase A Inhibitors

Inmaculada Rentero Rebollo

Bicyclic peptide ligands are promising molecules for the development of new therapeutics. They combine advantages from large protein therapeutics and small molecule drugs. Large combinatorial libraries of bicyclic peptides can be generated and screened by phage display using a recently developed strategy. Potent and selective bicyclic peptide inhibitors against several therapeutic targets have already been developed and their therapeutic potential is currently being evaluated in animal models. One aim of my thesis was the exploration of ring size diversity in bicyclic peptides. I generated a set of libraries of the format Cys-(Xaa)m-Cys-(Xaa)n-Cys, where 'm' and 'n' = 3, 4, 5 or 6, and performed affinity selections against the serine protease urokinase-type plasminogen activator. Bicyclic peptide inhibitors from virtually all ring size combinations were isolated, suggesting that many peptide formats can be accommodated in the active site of this enzyme. Moreover, they showed a large variety of consensus sequences and several of the identified consensus sequences were exclusively found in bicyclic peptides having specific ring size combinations. Having available multiple leads isolated from such bicyclic peptide libraries with variable ring sizes could be a great asset for the generation of high affinity binders. Additionally, other targets may have preferences for specific peptide constraints and the availability of these libraries increases the chances to isolate high affinity binders to any desired target. A second goal of my thesis was to apply high throughput sequencing technologies to phage display selections of bicyclic peptides, in order to identify a larger number of specific target-binding sequences and motifs. I developed a procedure to efficiently compare the sequences of large numbers of phage-selected peptides to identify target-binding peptide motifs based on abundance and sequence similarity. Applying this approach to phage isolated in selections against five different protein targets, I was able to identify rare target-binding peptide motifs and could more precisely define groups and sub-groups of consensus sequences. This information is valuable to choose peptide leads for drug development and facilitates the identification of epitopes. Moreover, binding motifs could be identified after a single round of phage panning. The final aim of my thesis was to discover bicyclic peptides that could be used as new antibiotics. Towards this end, I combined the newly generated variable ring size libraries and high-throughput sequencing procedures. I focused on the development of inhibitors of Staphylococcus aureus sortase A, an antivirulence target for which no potent and specific inhibitors have been reported. For the isolation of bicyclic peptide inhibitors to this target, the ring size diversity of the libraries turned out to be key. Inhibitors all shared the same motif in a loop of 5 residues. Further characterization of their effects on S. aureus showed that they could inhibit sortase-mediated incorporation of external substrates on the staphylococcal cell wall. However, they were not sufficiently potent to compete with the native substrates of the enzyme. More potent inhibitors are needed to effectively inhibit sortase A on S. aureus cells, and the bicyclic peptide inhibitors isolated constitute promising leads for the development of future antisortase therapeutics.

EPFL2014

Improving Bicyclic Peptide Phage Display and Development of Sortase A Inhibitors

Inmaculada Rentero Rebollo

EPFL2014