Durch umfassende Expressionsstudien zu einem tieferen Verstaendniss einer Pseudomonas aeruginosa Infektion: Von Modellen und realen Infektionsbedingungen zu moeglichen Behandlungsstrategien

Pseudomonas aeruginosa is a threatening opportunistic pathogen that causes severe acute and chronic infections in immunocompromised patients. Global transcriptomic analysis of P. aeruginosa infecting various hosts was carried out. In vivo gene expression was successfully performed by developing accurate, specific technical procedures. The transcriptomic analysis suggested that the main factors expressed by P. aeruginosa upon infection of burn wounds are iron and zinc acquisition as well as alginate production. The bacterial state during burn wound infection was not fully acute, with bacterial cells undergoing serious iron limitation and having a slower metabolism. Iron acquisition and alginate production were shown to be important mechanisms common among the infection conditions studied, namely burn wound, CF patient and mouse tumour model. Two models for P. aeruginosa infection were tested. The tumour mouse model is a promising mammalian infection model whereby P. aeruginosa exhibits anaerobic growth, biofilm formation and expresses the type III secretion system. This model is being further tested in order to assess if it can be used as a chronic infection model. The plant infection model using lettuce leaves may be useful for the study of certain factors such as QS systems, but yielded different results as compared to the real mammalian infections and cannot therefore be used as a reliable infection model. The analysis of the gene expression data from the work presented here thus provided a wealth of new insights and established a foundation for future work directed at the understanding of P. aeruginosa infection and at finding new prevention and treatment strategies.Pseudomonas aeruginosa ist ein bedrohlicher opportunistischer Krankheitserreger, der bei immunsupprimierten Patienten schwerwiegende akute und chronische Infektionen hervorrufen kann. Eine umfassende Transkriptomanalyse von P. aeruginosa bei der Infektion verschiedener Wirte wurde durchgeführt. Die Messungen erfolgten unter in vivo Bedingungen, was die Entwicklung von präzisen und spezifischen technischen Verfahren voraussetzte. Die Transkriptomanalyse deutete darauf hin, dass die Eisen- und Zinkaufnahme und die Alginatproduktion die Hauptfaktoren sind, die von P. aeruginosa während Brandwundeninfektion exprimiert werden. Der bakterielle Zustand während einer Brandwundeninfektion war nicht ganz akut; die Bakterienzellen wurden einem erheblichen Mangel an Eisen ausgesetzt und weisen einen varlangsamten Stoffwechsel auf. Eisenaufnahme und Alginatproduktion erwiesen sich als wichtige Mechanismen, die unter den untersuchten Infektionsbedingungen, nämlich im Fall von Brandwunden, CF-Patienten und Maustumormodellen, verbreitet sind. Es wurden zwei Modelle für die P. aeruginosa Infektion untersucht. Das Tumor-Mausmodell ist ein vielversprechendes Säugetierinfektionsmodell, wobei P. aeruginosa anaerobes Wachstum und Biofilmbildung aufweist und das Typ III-Sekretionssystem exprimiert. Dieses Modell wird weiterhin untersucht, um herauszufinden, ob es als Modell für chronische Infektionen dienen kann. Das Pflanzeninfektionsmodell, wobei Salatblätter eingesetzt werden, könnte von Nutzen sein, um bestimmte Faktoren, wie das QS-System, zu untersuchen, führte jedoch zu anderen Ergebnissen als bei den Säugetierinfektionen und kann daher nicht als verlässliches Infektionsmodell eingesetzt werden. Die Analyse der Genexpressionsdaten aus der hier vorgestellten Arbeit hat eine Fülle neuer Kenntnisse ergeben und Grundlagen für zukünftige Forschungsarbeiten geschaffen, die darauf abzielen, P. aeruginosa-Infektionen zu verstehen und neue Präventions- und Behandlungsstrategien zu finden

Diminished production of TWEAK by the peripheral blood mononuclear cells is associated with vascular involvement in patients with systemic sclerosis.

Widespread vasculopathy and profound fibrosis are key features of the pathogenesis of systemic sclerosis (SSc). We hypothesized that the TNF-like weak inducer of apoptosis (TWEAK), a recently recognized multifunctional cytokine which regulates angiogenesis and tissue remodeling, may play a role in the development of SSc. The production of TWEAK by the peripheral blood mononuclear cells (PBMC) was investigated, by means of ELISA, in 24 SSc patients and 14 healthy subjects. Moreover, production of TWEAK was correlated with clinical features of SSc. PBMC were isolated using density gradient centrifugation on Histopaque and were cultured in FCS supplemented RPMI medium at 37 degrees C under 5% CO2. Production of TWEAK by PBMC was significantly diminished in patients with more severe microvascular damage, as indicated by the presence of "active" capillaroscopic pattern, compared with SSc patients with less pronounced microangiopathy ("slow" pattern), and healthy subjects. Moreover production of TWEAK correlated inversely with duration of Raynaud's phenomenon. PBMC from patients with scleroderma-related interstitial lung disease tended to produce lower amounts of TWEAK compared with SSc patients without lung involvement but the difference was not significant. The results of our study suggest that diminished production of TWEAK might play a role in the pathogenesis of vascular injury in SSc patients. Whether TWEAK may represent a new therapeutic target in SSc requires further studies

Molecular aspects of bacterial nanocellulose biosynthesis

Bacterial nanocellulose (BNC) produced by aerobic bacteria is a biopolymer with sophisticated technical properties. Although the potential for economically relevant applications is huge, the cost of BNC still limits its application to a few biomedical devices and the edible product Nata de Coco, made available by traditional fermentation methods in Asian countries. Thus, a wider economic relevance of BNC is still dependent on breakthrough developments on the production technology. On the other hand, the development of modified strains able to overproduce BNC with new properties e.g. porosity, density of fibres crosslinking, mechanical properties, etc. will certainly allow to overcome investment and cost production issues and enlarge the scope of BNC applications. This review discusses current knowledge about the molecular basis of BNC biosynthesis, its regulations and, finally, presents a perspective on the genetic modification of BNC producers made possible by the new tools available for genetic engineering.(undefined)info:eu-repo/semantics/publishedVersio

Taxonomic review and microbial ecology in bacterial nanocellulose fermentation

Acetic acid bacteria (AAB) have a long history of use in several fermentation processes. Their exploitation gradually emerged in biotechnologic applications, especially in the biosynthesis of useful chemicals and processes for the manufacture of several fermented food products. Taxonomic studies, from traditional to polyphasic approaches, have gradually allowed the proper classification of several ABB into distinct genera and species, among them, the bacterial nanocellulose (BNC) producers, notably Komagataeibacter xylinus. Despite the advantages in using specific (isolated) strains for biotechnologic processes toward controlling the kinetics and process yield, mixed culture fermentations may provide an interesting approach to tailoring the properties of BNC and to increase the product yield when aiming at industrial scale. Microbial population dynamics may play a synergistic role in the coordinative substrate consumption and metabolites production, especially if using complex media (as is the case with low cost substrates, eg, residues from other processes). This chapter will first review the main historic steps involved in the taxonomic classification of AAB. It will then address the lying potential behind mixed microbial fermentations, from kombucha to nata de coco, both sharing in common, the contribution of cellulose-producing bacteria for the fermentation process.(undefined

Diminished production of TWEAK by the peripheral blood mononuclear cells is associated with vascular involvement in patients with systemic sclerosis.

Widespread vasculopathy and profound fibrosis are key features of the pathogenesis of systemic sclerosis (SSc). We hypothesized that the TNF-like weak inducer of apoptosis (TWEAK), a recently recognized multifunctional cytokine which regulates angiogenesis and tissue remodeling, may play a role in the development of SSc. The production of TWEAK by the peripheral blood mononuclear cells (PBMC) was investigated, by means of ELISA, in 24 SSc patients and 14 healthy subjects. Moreover, production of TWEAK was correlated with clinical features of SSc. PBMC were isolated using density gradient centrifugation on Histopaque and were cultured in FCS supplemented RPMI medium at 37 degrees C under 5% CO2. Production of TWEAK by PBMC was significantly diminished in patients with more severe microvascular damage, as indicated by the presence of "active" capillaroscopic pattern, compared with SSc patients with less pronounced microangiopathy ("slow" pattern), and healthy subjects. Moreover production of TWEAK correlated inversely with duration of Raynaud's phenomenon. PBMC from patients with scleroderma-related interstitial lung disease tended to produce lower amounts of TWEAK compared with SSc patients without lung involvement but the difference was not significant. The results of our study suggest that diminished production of TWEAK might play a role in the pathogenesis of vascular injury in SSc patients. Whether TWEAK may represent a new therapeutic target in SSc requires further studies

Efficient method for transport simulations in quantum cascade lasers

An efficient method for simulating quantum transport in quantum cascade lasers is presented. The calculations are performed within a simple approximation inspired by Büttiker probes and based on a finite model for semiconductor superlattices. The formalism of non-equilibrium Green’s functions is applied to determine the selected transport parameters in a typical structure of a terahertz laser. Results were compared with those obtained for a infinite model as well as other methods described in literature