Peptides as potent antimicrobials tethered to a solid surface: Implications for medical devices

Medical devices are an integral part of therapeutic management; despite their importance, they carry a significant risk of microbial infection. Bacterial attachment to a medical device is established by a single, multiplying organism, leading to subsequent biofilm formation. To date, no preventative measures have impacted the incidence of device-related infection. We report the bidirectional covalent coupling of an engineered cationic antimicrobial peptide (eCAP), WLBU2, to various biological surfaces is accomplished. These surfaces included (i) a carbohydrate-based gel matrix, (ii) a complex polymeric plastic bead, and (iii) a silica-calcium phosphate nanocomposite associated with bone reconstruction. WLBU2-conjugated surfaces are shown to retain potent antimicrobial activity related to bacterial surface adhesion. This study provides proof of principle that covalently coating laboratory and bone-regenerating materials with eCAPs has the potential for decreasing infection rates of implanted devices. These findings have important consequences to the patient management component of our current health care technology

It’s Not Only Rents: Explaining the Persistence and Change of Neopatrimonialism in Indonesia

Indonesia has long been associated with neopatrimonialism, corruption, collusion, and nepotism as the main modi operandi of politics, economics and public administration. Despite various measures and initiatives to fight these practises, little evidence for a significant decline can be found over the years. Rather, longitudinal analysis points to changes in the character of neopatrimonialism. Based on more than 60 in-depth interviews, focus-group discussions, and the analysis of both primary and secondary data, the aim of this article is, first, to describe the changes that have taken place, and, second, to investigate what accounts for these changes. Political economy concepts posit the amount and development of economic rents as the explanatory factor for the persistence and change of neopatrimonialism. This study's findings, however, indicate that rents alone cannot explain what has taken place in Indonesia. Democratisation and decentralisation exert a stronger impact

The hFbpABC Transporter from Haemophilus influenzae Functions as a Binding-Protein-Dependent ABC Transporter with High Specificity and Affinity for Ferric Iron

Pathogenic Haemophilus influenzae, Neisseria spp. (Neisseria gonorrhoeae and N. meningitidis), Serratia marcescens, and other gram-negative bacteria utilize a periplasm-to-cytosol FbpABC iron transporter. In this study, we investigated the H. influenzae FbpABC transporter in a siderophore-deficient Escherichia coli background to assess biochemical aspects of FbpABC transporter function. Using a radiolabeled Fe(3+) transport assay, we established an apparent K(m) = 0.9 μM and V(max) = 1.8 pmol/10(7)cells/min for FbpABC-mediated transport. Complementation experiments showed that hFbpABC is dependent on the FbpA binding protein for transport. The ATPase inhibitor sodium orthovanadate demonstrated dose-dependent inhibition of FbpABC transport, while the protonmotive-force-inhibitor carbonyl cyanide m-chlorophenyl hydrazone had no effect. Metal competition experiments demonstrated that the transporter has high specificity for Fe(3+) and selectivity for trivalent metals, including Ga(3+) and Al(3+), over divalent metals. Metal sensitivity experiments showed that several divalent metals, including copper, nickel, and zinc, exhibited general toxicity towards E. coli. Significantly, gallium-induced toxicity was specific only to E. coli expressing FbpABC. A single-amino-acid mutation in the gene encoding the periplasmic binding protein, FbpA(Y196I), resulted in a greatly diminished iron binding affinity K(d) = 5.2 × 10(−4) M(−1), ∼14 orders of magnitude weaker than that of the wild-type protein. Surprisingly, the mutant transporter [FbpA(Y196I)BC] exhibited substantial transport activity, ∼35% of wild-type transport, with K(m) = 1.2 μM and V(max) = 0.5 pmol/10(7)cells/min. We conclude that the FbpABC complexes possess basic characteristics representative of the family of bacterial binding protein-dependent ABC transporters. However, the specificity and high-affinity binding characteristics suggest that the FbpABC transporters function as specialized transporters satisfying the strict chemical requirements of ferric iron (Fe(3+)) binding and membrane transport