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61.
Ocellatin‐PT antimicrobial peptides: High‐resolution microscopy studies in antileishmania models and interactions with mimetic membrane systems
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Mayara Oliveira Ana Georgina Gomes‐Alves Carla Sousa Mariela Mirta Marani Alexandra Plácido Nuno Vale Cristina Delerue‐Matos Paula Gameiro Selma A. S. Kückelhaus Ana M. Tomas José Roberto S. A. Leite Peter Eaton 《Biopolymers》2016,105(12):873-886
Although the mechanism of action of antimicrobial peptides (AMPs) is not clear, they can interact electrostatically with the cell membranes of microorganisms. New ocellatin‐PT peptides were recently isolated from the skin secretion of Leptodactylus pustulatus. The secondary structure of these AMPs and their effect on Leishmania infantum cells, and on different lipid surface models was characterized in this work. The results showed that all ocellatin‐PT peptides have an α‐helix structure and five of them (PT3, PT4, PT6 to PT8) have leishmanicidal activity; PT1 and PT2 affected the cellular morphology of the parasites and showed greater affinity for leishmania and bacteria‐mimicking lipid membranes than for those of mammals. The results show selectivity of ocellatin‐PTs to the membranes of microorganisms and the applicability of biophysical methods to clarify the interaction of AMPs with cell membranes. 相似文献
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Frank Lennartz Karen Bayer Nadine Czerwonka Yinghui Lu Kristine Kehr Manuela Hirz Torsten Steinmetzer Wolfgang Garten Christiane Herden 《Cellular microbiology》2016,18(3):340-354
Borna disease virus (BDV) is a non‐segmented negative‐stranded RNA virus that maintains a strictly neurotropic and persistent infection in affected end hosts. The primary target cells for BDV infection are brain cells, e.g. neurons and astrocytes. The exact mechanism of how infection is propagated between these cells and especially the role of the viral glycoprotein (GP) for cell–cell transmission, however, are still incompletely understood. Here, we use different cell culture systems, including rat primary astrocytes and mixed cultures of rat brain cells, to show that BDV primarily spreads through cell–cell contacts. We employ a highly stable and efficient peptidomimetic inhibitor to inhibit the furin‐mediated processing of GP and demonstrate that cleaved and fusion‐active GP is strictly necessary for the cell‐to‐cell spread of BDV. Together, our quantitative observations clarify the role of Borna disease virus‐glycoprotein for viral dissemination and highlight the regulation of GP expression as a potential mechanism to limit viral spread and maintain persistence. These findings furthermore indicate that targeting host cell proteases might be a promising approach to inhibit viral GP activation and spread of infection. 相似文献
64.
Genes,symptoms, and the “asymptomatic ill”: toward a broader understanding of genetic discrimination
Tino Plümecke 《New genetics and society》2016,35(2):124-148
Since the early 1990s, the term “genetic discrimination” has been used to designate adverse treatment on the grounds of genetic makeup. However, the full spectrum of possible disadvantage associated with genetic information has not been addressed by either the international scientific debate or statutory arrangements on genetic discrimination. Informed by legal contexts, they almost all focus on one specific group: the “asymptomatic ill.” On the basis of the sociological study, “Genetic Discrimination in Germany,” this article proposes to revise the terms of the debate and discusses some limitations of the concept. Drawing on the experiences reported by affected individuals, it advocates a more expansive social understanding which does not require that a person has to be healthy to be at risk of genetic discrimination. 相似文献
65.
Erzsebet Pászti-Gere Réka Fanni Barna Gabriella Ujhelyi Torsten Steinmetzer 《Journal of enzyme inhibition and medicinal chemistry》2016,31(5):736-741
The type II trypsin-like transmembrane serine protease matriptase, is mainly expressed in epithelial cells and one of the key regulators in the formation and maintenance of epithelial barrier integrity. Therefore, we have studied the inhibition of matriptase in a non-transformed porcine intestinal IPEC-J2 cell monolayer cultured on polyester membrane inserts by the non-selective 4-(2-aminoethyl)-benzosulphonylfluoride (AEBSF) and four more selective 3-amidinophenylalanine-derived matriptase inhibitors. It was found that suppression of matriptase activity by MI-432 and MI-460 led to decreased transepithelial electrical resistance (TER) of the cell monolayer and to an enhanced transport of fluorescently labelled dextran, a marker for paracellular transport between apical and basolateral compartments. To this date this is the first report in which the inhibition of matriptase activity by synthetic inhibitors has been correlated to a reduced barrier integrity of a non-cancerous IPEC-J2 epithelial cell monolayer in order to describe interaction between matriptase activity and intestinal epithelium in vitro. 相似文献
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Torsten Schubert Stephan H. von Reuß Cindy Kunze Christian Paetz Stefan Kruse Peggy Brand-Schön Anita Mac Nelly Jörg Nüske Gabriele Diekert 《Microbial biotechnology》2019,12(2):346-359
Cobamides (Cbas) are essential cofactors of reductive dehalogenases (RDases) in organohalide-respiring bacteria (OHRB). Changes in the Cba structure can influence RDase function. Here, we report on the cofactor versatility or selectivity of Desulfitobacterium RDases produced either in the native organism or heterologously. The susceptibility of Desulfitobacterium hafniense strain DCB-2 to guided Cba biosynthesis (i.e. incorporation of exogenous Cba lower ligand base precursors) was analysed. Exogenous benzimidazoles, azabenzimidazoles and 4,5-dimethylimidazole were incorporated by the organism into Cbas. When the type of Cba changed, no effect on the turnover rate of the 3-chloro-4-hydroxy-phenylacetate-converting enzyme RdhA6 and the 3,5-dichlorophenol-dehalogenating enzyme RdhA3 was observed. The impact of the amendment of Cba lower ligand precursors on RDase function was also investigated in Shimwellia blattae, the Cba producer used for the heterologous production of Desulfitobacterium RDases. The recombinant tetrachloroethene RDase (PceAY51) appeared to be non-selective towards different Cbas. However, the functional production of the 1,2-dichloroethane-dihaloeliminating enzyme (DcaA) of Desulfitobacterium dichloroeliminans was completely prevented in cells producing 5,6-dimethylbenzimidazolyl-Cba, but substantially enhanced in cells that incorporated 5-methoxybenzimidazole into the Cba cofactor. The results of the study indicate the utilization of a range of different Cbas by Desulfitobacterium RDases with selected representatives apparently preferring distinct Cbas. 相似文献
68.
Santini Nadia S. Lovelock Catherine E. Hua Quan Zawadzki Atun Mazumder Debashish Mercer Tim R. Muñoz-Rojas Miriam Hardwick Simon A. Madala Bindu Swapna Cornwell William Thomas Torsten Marzinelli Ezequiel M. Adam Paul Paul Swapan Vergés Adriana 《Ecosystems》2019,22(8):1803-1822
Ecosystems - Saltmarshes provide many valuable ecosystem services including storage of a large amount of ‘blue carbon’ within their soils. To date, up to 50% of the world’s... 相似文献
69.
Franziska S. Kemter Nadine Schallopp Theodor Sperlea Javier Serrania Patrick Sobetzko Georg Fritz Torsten Waldminghaus 《Molecular microbiology》2019,111(6):1617-1637
Vibrio cholerae is an aquatic bacterium with the potential to infect humans and cause the cholera disease. While most bacteria have single chromosomes, the V. cholerae genome is encoded on two replicons of different size. This study focuses on the DNA replication and cell division of this bi‐chromosomal bacterium during the stringent response induced by starvation stress. V. cholerae cells were found to initially shut DNA replication initiation down upon stringent response induction by the serine analog serine hydroxamate. Surprisingly, cells temporarily restart their DNA replication before finally reaching a state with fully replicated single chromosome sets. This division‐replication pattern is very different to that of the related single chromosome model bacterium Escherichia coli. Within the replication restart phase, both chromosomes of V. cholerae maintained their known order of replication timing to achieve termination synchrony. Using flow cytometry combined with mathematical modeling, we established that a phase of cellular regrowth be the reason for the observed restart of DNA replication after the initial shutdown. Our study shows that although the stringent response induction itself is widely conserved, bacteria developed different ways of how to react to the sensed nutrient limitation, potentially reflecting their individual lifestyle requirements. 相似文献