Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base

Hamiltonian cycles in the generating graphs of finite groups

For a finite group G let Gamma(G) denote the graph defined on the non-identity elements of G in such a way that two distinct vertices are connected by an edge if and only if they generate G. In this paper it is shown that the graph Gamma(G) contains a Hamiltonian cycle for many finite groups G

pH-sensitive fluorescent dye as probe for proton uptake in photosynthetic reaction centers

Isolated and purified reaction centers (RC) from Rhodobacter sphaeroides R-26.1 were solubilised in detergent with excess quinone and external electron donors and illuminated in the presence of pyranine. The pH change accompanying the reaction center photocycle was monitored by recording the variation of the pyranine fluorescence intensity. Using QB-depleted reaction centers or blocking the photocycle with terbutryne strongly reduced the pH change. The usefulness and limits of this technique in monitoring the pH changes during the RC photocycle are also discussed

pH-sensitive fluorescent dye as probe for proton uptake in photosynthetic reaction centers

Isolated and purified reaction centers (RC) from Rhodobacter sphaeroides R-26.1 were solubilised in detergent with excess quinone and external electron donors and illuminated in the presence of pyranine. The pH change accompanying the reaction center photocycle was monitored by recording the variation of the pyranine fluorescence intensity. Using Q(B)-depleted reaction centers or blocking the photocycle with terbutryne strongly reduced the pH change. The usefulness and limits of this technique in monitoring the pH changes during the RC photocycle are also discussed

Reaction centers in lipids

Specific functional role of physiologically important lipids of the photosynthetic membrane (phosphatidylcholine, cardiolipin and phosphatidylglycerol) was investigated on the thermodynamic and kinetic requirements of the charge movements in bacterial reaction centers. The major effect of these lipids is to increase the stabilization of the separated caharges induced by light excitation during the photosynthetic energy conversion. It can be achieved by (1) changing the redox midpoint potential of the QA/QA- and QB/QB- redox couples, which results in the increase of the free energy gap that drives the QA– to QB electron transfer or (2) by changing the quinone binding/unbinding equilibrium. This study provides evidence that from kinetic point of view the P+QA-QB P+QAQB- charge transfer is mainly driven by the change in the enthalpy in LDAO and PC, whereas the entropy contribution is larger if negatively charged lipids are introduced

Light induced transmembrane proton gradient in artificial lipid vesicles reconstituted with photosynthetic reaction centers

Photosynthetic reaction center (RC) is the minimal nanoscopic photoconverter in the photosynthetic membrane that catalyzes the conversion of solar light to energy readily usable for the metabolism of the living organisms. After electronic excitation the energy of light is converted into chemical potential by the generation of a charge separated state accompanied by intraprotein and ultimately transmembrane proton movements. We designed a system which fulfills the minimum structural and functional requirements to investigate the physico/chemical conditions of the processes: RCs were reconstituted in closed lipid vesicles made of selected lipids entrapping a pH sensitive indicator, and electron donors (cytochrome c(2) and K-4[Fe(CN)(6)]) and acceptors (decylubiquinone) were added to sustain the photocycle. Thanks to the low proton permeability of our preparations, we could show the formation of a transmembrane proton gradient under illumination and low buffering conditions directly by measuring proton-related signals simultaneously inside and outside the vesicles. The effect of selected ionophores such as gramicidin, nigericin and valinomycin was used to gain more information on the transmembrane proton gradient driven by the RC photochemistry

Enthalpy/entropy driven activation of the first interquinone electron transfer in bacterial photosynthetic reaction centers embedded in vesicles of physiologically important phospholipids.

The thermodynamics and kinetics of light-induced electron transfer in bacterial photosynthetic RCs are sensitive to physiologically important lipids (phosphatidylcholine, cardiolipin and phosphatidylglycerol) in the environment. The analysis of the temperature-dependence of the rate of the P(+)Q(A)(-)Q(B)-->P(+)Q(A)Q(B)(-) interquinone electron transfer revealed high enthalpy change of activation in zwitterionic or neutral micelles and vesicles and low enthalpy change of activation in vesicles constituted of negatively charged phospholipids. The entropy change of activation was compensated by the changes of enthalpy, thus the free energy change of activation ( approximately 500 meV) did not show large variation in vesicles of different lipids