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- Galka, Frank, et al.
(författare)
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Proteomic characterization of the whole secretome of Legionella pneumophila and functional analysis of outer membrane vesicles.
- 2008
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Ingår i: Infection and immunity. - 1098-5522. ; 76:5, s. 1825-36
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Tidskriftsartikel (refereegranskat)abstract
- Secretion of effector molecules is one of the major mechanisms by which the intracellular human pathogen Legionella pneumophila interacts with host cells during infection. Specific secretion machineries which are responsible for the subfraction of secreted proteins (soluble supernatant proteins [SSPs]) and the production of bacterial outer membrane vesicles (OMVs) both contribute to the protein composition of the extracellular milieu of this lung pathogen. Here we present comprehensive proteome reference maps for both SSPs and OMVs. Protein identification and assignment analyses revealed a total of 181 supernatant proteins, 107 of which were specific to the SSP fraction and 33 of which were specific to OMVs. A functional classification showed that a large proportion of the identified OMV proteins are involved in the pathogenesis of Legionnaires' disease. Zymography and enzyme assays demonstrated that the SSP and OMV fractions possess proteolytic and lipolytic enzyme activities which may contribute to the destruction of the alveolar lining during infection. Furthermore, it was shown that OMVs do not kill host cells but specifically modulate their cytokine response. Binding of immunofluorescently stained OMVs to alveolar epithelial cells, as visualized by confocal laser scanning microscopy, suggested that there is delivery of a large and complex group of proteins and lipids in the infected tissue in association with OMVs. On the basis of these new findings, we discuss the relevance of protein sorting and compartmentalization of virulence factors, as well as environmental aspects of the vesicle-mediated secretion.
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| 2. |
- Pagels, Martin, et al.
(författare)
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Redox sensing by a Rex-family repressor is involved in the regulation of anaerobic gene expression in Staphylococcus aureus
- 2010
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Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 76:5, s. 1142-1161
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Tidskriftsartikel (refereegranskat)abstract
- P>An alignment of upstream regions of anaerobically induced genes in Staphylococcus aureus revealed the presence of an inverted repeat, corresponding to Rex binding sites in Streptomyces coelicolor. Gel shift experiments of selected upstream regions demonstrated that the redox-sensing regulator Rex of S. aureus binds to this inverted repeat. The binding sequence - TTGTGAAW(4)TTCACAA - is highly conserved in S. aureus. Rex binding to this sequence leads to the repression of genes located downstream. The binding activity of Rex is enhanced by NAD+ while NADH, which competes with NAD+ for Rex binding, decreases the activity of Rex. The impact of Rex on global protein synthesis and on the activity of fermentation pathways under aerobic and anaerobic conditions was analysed by using a rex-deficient strain. A direct regulatory effect of Rex on the expression of pathways that lead to anaerobic NAD+ regeneration, such as lactate, formate and ethanol formation, nitrate respiration, and ATP synthesis, is verified. Rex can be considered a central regulator of anaerobic metabolism in S. aureus. Since the activity of lactate dehydrogenase enables S. aureus to resist NO stress and thus the innate immune response, our data suggest that deactivation of Rex is a prerequisite for this phenomenon.
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| 3. |
- Geisler, Ursula, et al.
(författare)
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Musik baut Brücken? Über Bedingungen und Schwierigkeiten transnationaler Kulturforschung
- 2010
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Ingår i: Vom alten Norden zum neuen Europa: Politische Kultur im Ostseeraum. Festschrift für Bernd Henningsen. - 9783830517818 ; , s. 409-422
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This contribution deals with the topic of transnationalism as it has developed in the humanities in the last two decades. The starting point for the reflections is the author's experiences over the course of two research projects in the years 1996 to 2003. "Musik baut Brücken?" seeks to highlight some of the definitions and difficulties of "transnationalism" which have become obvious in several debates and in research projects. Employing illuminating, empirical examples, this text pays particular attention to music, folk songs and community singing from a Swedish-German perspective.
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| 4. |
- Gómez-Fernández, Paloma, et al.
(författare)
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The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10-4). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%-60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS.
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| 9. |
- Reinthaler, Eva M., et al.
(författare)
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TPP2 mutation associated with sterile brain inflammation mimicking MS
- 2018
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Ingår i: NEUROLOGY-GENETICS. - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective To ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS.Methods We used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan.Results In this study, we describe the identification of a homozygous missense mutation (c.82T>G, p.Cys28Gly) in the tripeptidyl peptidase II (TPP2) gene in all 3 affected siblings of the family. Sequencing of all TPP2-coding exons in 826 MS cases identified one further homozygous missense variant (c.2027C>T, p.Thr676Ile) in a Jordanian MS patient. TPP2 protein expression in whole blood was reduced in the affected siblings. In contrast, TPP2 protein expression in postmortem brain tissue from MS patients without TPP2 mutations was highly upregulated.Conclusions The homozygous TPP2 mutation (p.Cys28Gly) is likely responsible for the inflammation phenotype in this family. TPP2 is an ubiquitously expressed serine peptidase that removes tripeptides from the N-terminal end of longer peptides. TPP2 is involved in various biological processes including the destruction of major histocompatibility complex Class I epitopes. Recessive loss-of-function mutations in TPP2 were described in patients with Evans syndrome, a rare autoimmune disease affecting the hematopoietic system. Based on the gene expression results in our MS autopsy brain samples, we further suggest that TPP2 may play a broader role in the inflammatory process in MS.
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| 10. |
- Song, Renfang, et al.
(författare)
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Effects of fifteen PBDE metabolites, DE71, DE79 and TBBPA on steroidogenesis in the H295R cell line
- 2008
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 71:10, s. 1888-1894
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs) and tetrabromobisphenol A (TBBPA) are brominated flame retardants that are produced in large quantities and are commonly used in construction materials, textiles, and as polymers in electronic equipment. Environmental and human levels of PBDEs have been increasing in the past 30 years, but the toxicity of PBDEs is not fully understood. Studies on their effects are relatively limited, and show that PBDEs are neurotoxins and potential endocrine disrupters. Hydroxylated (OH{single bond}) and methoxylated (MeO{single bond}) PBDEs have also been reported in the adipose tissue, blood and milk of wild animals and humans. In the present study, 15 PBDE metabolites, two BDE mixtures (DE71 and DE79), and TBBPA were studied individually to determine their effects on ten steroidogenic genes, aromatase activity, and concentrations of two steroid hormones (testosterone and 17β-estradiol) in the H295R human adrenocortical carcinoma cell line. Exposure to 0.05 μM 2′-OH-BDE-68 significantly induced the expression of CYP11A, CYP11B2, CYP17, CYP21, 3βHSD2, 17βHSD1, and 17βHSD4, and the expression of StAR was induced by 6-OH-BDE-90 at the three exposure concentrations. Exposure to DE71 and DE79 resulted in dose-dependent trend towards induction, but these effects were not significant. Exposure to 0.5 μM 2-OH-BDE-123 and 2-MeO-BDE-123 resulted in significantly greater aromatase activity. However, none of the compounds affected sex hormone production at the concentrations tested. Generally, OH-BDEs had a much stronger ability to affect steroidogenic gene expression than MeO-BDEs.
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