Strategies to Tackle Antimicrobial Resistance: The Example of Escherichia coli and Pseudomonas aeruginosa

Traditional antimicrobial treatments consist of drugs which target different essential functions in pathogens. Nevertheless, bacteria continue to evolve new mechanisms to evade this drug-mediated killing with surprising speed on the deployment of each new drug and antibiotic worldwide, a phenomenon called antimicrobial resistance (AMR). Nowadays, AMR represents a critical health threat, for which new medical interventions are urgently needed. By 2050, it is estimated that the leading cause of death will be through untreatable AMR pathogens. Although antibiotics remain a first-line treatment, non-antibiotic therapies such as prophylactic vaccines and therapeutic monoclonal antibodies (mAbs) are increasingly interesting alternatives to limit the spread of such antibiotic resistant microorganisms. For the discovery of new vaccines and mAbs, the search for effective antigens that are able to raise protective immune responses is a challenging undertaking. In this context, outer membrane vesicles (OMV) represent a promising approach, as they recapitulate the complete antigen repertoire that occurs on the surface of Gram-negative bacteria. In this review, we present Escherichia coli and Pseudomonas aeruginosa as specific examples of key AMR threats caused by Gram-negative bacteria and we discuss the current status of mAbs and vaccine approaches under development as well as how knowledge on OMV could benefit antigen discovery strategies.     

Sugar‐Based Arylsulfonamide Carboxylates as Selective and Water‐Soluble Matrix Metalloproteinase‐12 Inhibitors

Matrix metalloproteinase‐12 (MMP‐12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a new series of arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation with a β‐N‐acetyl‐d ‐glucosamine moiety, were designed and synthesized as MMP‐12 selective inhibitors. Their inhibitory activity was evaluated on human MMPs by using the fluorimetric assay, and a crystallographic analysis was performed to characterize their binding mode. Among these glycoconjugates, a nanomolar MMP‐12 inhibitor with improved water solubility, compound 3 [(R)‐2‐(N‐(2‐(3‐(2‐acetamido‐2‐deoxy‐β‐d ‐glucopyranosyl)thioureido)ethyl)biphenyl‐4‐ylsulfonamido)‐3‐methylbutanoic acid], was identified.     

Mn influence on the electrochemical behaviour of Li3V2(PO4)3 cathode material

The role played by the substitution of Mn on the electrochemical behaviour of Li₃V₂(PO₄)₃ has been investigated. Independently of the synthesis route, the Mn doping improves the electrochemical features with respect to the undoped samples. Different reasons can be taken into consideration to explain the electrochemical enhancement. In the sol–gel synthesis the capacity slightly enhances due to the Mn substitution on both the V sites, within the solubility limit x = 0.124 in Li₃V_2−xMn_x(PO₄)₃. In the solid state synthesis the significant capacity enhancement is preferentially due to the microstructural features of the crystallites and to the LiMnPO₄ phase formation.     

Optimizing Single‐Walled‐Carbon‐Nanotube‐Based Saturable Absorbers for Ultrafast Lasers

The application of single‐walled carbon nanotubes (SWCNTs) as saturable absorbers (SA) in a Nd:glass femtosecond laser is verified as a promising alternative to traditional semiconductor saturable‐absorber mirrors (SESAMs). The shortest laser pulses achieved with a SWCNT‐SA fabricated by the slow‐evaporation method are reported herein. Nearly Fourier‐limited 288 fs pulses are obtained with negative‐dispersion soliton mode‐locking. The importance of the properties of the starting material, such as the degree of purity and the chirality, and the successive slow‐evaporation deposition method is proven by using a multitechnique approach based on X‐ray diffractometry, scanning electron microscopy, and μ‐Raman spectroscopy. The high degree of nanotube alignment on the glass substrate and also the slight metallic character due to electron transfer between the glass matrix and the nanotubes themselves are identified as the main features responsible for the good laser response.     

The effect of rate of drying on the drying creep of hardened cement paste

Tests were performed on miniature, thin-wallm hardened cement paste specimens; specimens under load were dried at various rates, re-wet and then unloaded. Deformation was monitored throughout. Appropriate control specimens for shrinkage/swelling, basic creep and weight change were also tested. Relationships between moisture loss, shrinkage and wetting creep were obtained. It was found that, like shrinkage, the magnitude of drying creep is independent of rate of drying. Also, drying creep bears a linear relationship to concomitant shrinkage over a wide range; similarly, wetting creep is linearly related to swelling. Drying creep and wetting creep are completely irrecoverable. Discussion centres about the significance of the results with respect to the prediction of creep strains when environmental conditions change; results suggest it may be possible to develop prediction equations which are not overly complicated.     

Design and Synthesis of Ionic Liquid-Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI-Coated Gold Nanoparticles

Selective and potent matrix metalloproteinase 12 (MMP-12) inhibitors endowed with improved hydrophilicity are highly sought for potential use in the treatment of lung and cardiovascular diseases. In the present paper, we modified the structure of a nanomolar MMP-12 inhibitor by incorporating an ionic liquid (IL) moiety to improve aqueous solubility. Four biologically active salts were obtained by linking the sulfonamide moiety of the MMP-12 inhibitor to imidazolium-, pyrrolidinium-, piperidinium-, and DABCO-based ILs. The imidazolium-based bioactive salt was tested on human recombinant MMPs and on monocyte-derived dendritic cells, showing activity similar to that of the parent compound, but improved water solubility. The imidazolium-based bioactive salt was then used to prepare electrostatically stabilized MMP inhibitor-coated gold nanoparticles (AuNPs) able to selectively bind MMP-12. These AuNPs were used to study subcellular localization of MMP-12 in monocyte-derived dendritic cells by transmission electron microscopy analysis.