28 research outputs found

    NB2001, a Novel Antibacterial Agent with Broad-Spectrum Activity and Enhanced Potency against β-Lactamase-Producing Strains

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    Enzyme-catalyzed therapeutic activation (ECTA) is a novel prodrug strategy to overcome drug resistance resulting from enzyme overexpression. β-Lactamase overexpression is a common mechanism of bacterial resistance to β-lactam antibiotics. We present here the results for one of the β-lactamase ECTA compounds, NB2001, which consists of the antibacterial agent triclosan in a prodrug form with a cephalosporin scaffold. Unlike conventional β-lactam antibiotics, where hydrolysis of the β-lactam ring inactivates the antibiotic, hydrolysis of NB2001 by β-lactamase releases triclosan. Evidence supporting the proposed mechanism is as follows. (i) NB2001 is a substrate for TEM-1 β-lactamase, forming triclosan with a second-order rate constant (k(cat)/K(m)) of greater than 77,000 M(−1) s(−1). (ii) Triclosan is detected in NB2001-treated, β-lactamase-producing Escherichia coli but not in E. coli that does not express β-lactamase. (iii) NB2001 activity against β-lactamase-producing E. coli is decreased in the presence of the β-lactamase inhibitor clavulanic acid. NB2001 was similar to or more potent than reference antibiotics against clinical isolates of Staphylococcus aureus (including MRSA), Staphylococcus epidermidis, Streptococcus pneumoniae, vancomycin-resistant Enterococcus faecalis, Moraxella catarrhalis and Haemophilus influenzae. NB2001 is also active against Klebsiella pneumoniae, Enterobacter aerogenes, and Enterobacter cloacae. The results indicate that NB2001 is a potent, broad-spectrum antibacterial agent and demonstrate the potential of ECTA in overcoming β-lactamase-mediated resistance

    Titanium dioxide thin films deposition by direct current hollow cathode magnetron sputtering

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    Cylindrical hollow cathode magnetron sputtering (HCMS) system was used to deposit crystalline titanium dioxide thin films on p-Si (100) substrates. For a fixed pressure of 0.6 Pa total gas flow rate of 20 sccm and power of 55 W, the influence of the oxygen percentage in the Ar+O2 gas mixture on the structural and surface properties of the films was studied by profilometry, XRD and AFM. The substrates were placed inside the hollow cathode at different positions along its symmetrical axis. Numerical simulations of cathode ion collection probability (CICP) were done in order to compare calculated data with the deposition process characteristics. The results indicate that the deposition rate and the surface roughness gradually decrease with the distance from the bottom of the cathode, due to the decrease of the CICP. The increase of the oxygen percentage in the gas discharge influences directly the deposition rate and decrease the surface roughness. The XRD analyses show that all the films are crystalline with predominant anatase (101) and rutile (110) orientations

    Determining the origin and age of the Westland beech (Nothofagus) gap, New Zealand, using fungus beetle genetics

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    The formation and maintenance of the Nothofagus beech gap in the South Island, New Zealand, has been the focus of biogeographical debate since the 1920s. We examine the historical process of gap formation by investigating the population genetics of fungus beetles: Brachynopus scutellaris (Staphylinidae) inhabits logs and is absent from the beech gap, and Hisparonia hystrix (Nitidulidae) is contiguous through the gap and is found commonly on sooty mould growing on several plant species. Both species show distinctive northern and southern haplotype distributions while H. hystrix recolonized the gap as shown by definitive mixing. B. scutellaris shows two major haplotype clades with strong geographical concordance, and unlike H. hystrix, has clearly defined lineages that can be partitioned for molecular dating. Based on coalescence dating methods, disjunct lineages of B. scutellaris indicate that the gap was formed less than 200 000 years ago. Phylogenetic imprints from both species reveal similar patterns of population divergence corresponding to recent glacial cycles, favouring a glacial explanation for the origin of the gap. Post-gap colonization by H. hystrix may have been facilitated by the spread of Leptospermum scoparium host trees to the area, and they may be better at dispersing than B. scutellaris which may be constrained by fungal host and/or microhabitat. The gap-excluded species B. scutellaris is found in both beech and podocarp-broadleaf forests flanking the Westland gap and its absence in the gap may be related to incomplete recolonization following glacial retreat. We also discuss species status and an ancient polymorphism within B. scutellaris
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