| 1. |
- Frick, Inga-Maria, et al.
(författare)
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Uptake and intracellular transportation of a bacterial surface protein in lymphoid cells.
- 2002
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Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 44:4, s. 917-934
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Tidskriftsartikel (refereegranskat)abstract
- Some strains of the human pathogen Streptococcus pyogenes express a surface protein called protein H, which is released from the streptococcal surface by a cysteine proteinase produced by the bacteria. Here, we find that soluble protein H binds to the surface of lymphocytes and granulocytes, and that the molecule is taken up by lymphocytes and transported to the perinuclear region. The translocation over the cell membrane is rapid, and the uptake and intracellular transportation is not dependent on actin polymerization. Protein H could be immunoprecipitated from cell extracts and nuclear preparations of lymphocytes, and analysis of molecular interactions between pro-tein H and proteins of different cellular compart-ments demonstrated a binding to nucleophosmin/ B23, a protein known to shuttle between the cytoplasm and the nucleus, and to the nuclear proteins SET and hnRNP A2/B1. Nucleophosmin/B23 was co-immunoprecipitated with protein H from cell and nuclear extracts, and binding experiments, including kinetic analyses, suggest that protein H dissociating from nucleophosmin/B23 complexes in the perinuclear region or in the nucleus binds to proteins SET and hnRNP A2/B1. Finally, the uptake and intracellular transportation of protein H was found to result in a cytostatic effect on B and T lymphocytes.
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| 2. |
- Nordenfelt, Pontus, et al.
(författare)
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V-ATPase-mediated phagosomal acidification is impaired by Streptococcus pyogenes through Mga-regulated surface proteins.
- 2012
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1769-714X .- 1286-4579.
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes, a significant bacterial pathogen in humans, interferes with the membrane traffic of human neutrophils and survives following phagocytosis. The mechanism(s) behind this property is not known, but in contrast to wild-type bacteria, mutant bacteria lacking virulence factors regulated by the transcriptional regulator Mga, are phagocytosed and killed. In the present work we investigated whether differences in phagosomal acidification may contribute to this difference. Phagosomal pH in neutrophil-differentiated HL-60 cells was studied by fluorescence ratio imaging, and phagosomes containing wild-type S. pyogenes bacteria of the M1 serotype exhibited little or no acidification, whereas Mga mutant bacteria were found in more acidic phagosomes. With phagosomes containing these bacteria, proton delivery was inhibited by adding folimycin, a vacuolar-type adenosine triphosphatase (V-ATPase) inhibitor. This inhibitor had no effect on phagosomes containing wild-type bacteria, indicating either inactivation or removal of V-ATPases by the bacteria. Analysis of isolated bacteria-containing phagosomes confirmed the latter scenario and showed a more efficient delivery of V-ATPases to phagosomes containing Mga mutant bacteria. The results demonstrate that V-ATPase-mediated phagosomal proton delivery is reduced during phagocytosis of wild-type S. pyogenes, leading to impaired acidification, and that surface proteins of the mga regulon are responsible for this effect.
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| 3. |
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| 4. |
- Schmidtchen, Artur, et al.
(författare)
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Proteinases of common pathogenic bacteria degrade and inactivate the antibacterial peptide LL-37
- 2002
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Ingår i: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 46:1, s. 157-168
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Tidskriftsartikel (refereegranskat)abstract
- Effectors of the innate immune system, the anti-bacterial peptides, have pivotal roles in preventing infection at epithelial surfaces. Here we show that proteinases of the significant human pathogens Pseudomonas aeruginosa, Enterococcus faecalis, Proteus mirabilis and Streptococcus pyogenes, degrade the antibacterial peptide LL-37. Analysis by mass spectrometry of fragments generated by P. aeruginosa elastase in vitro revealed that the initial cleavages occurred at Asn-Leu and Asp-Phe, followed by two breaks at Arg-Ile, thus inactivating the peptide. Proteinases of the other pathogens also degraded LL-37 as determined by SDS-PAGE. Ex vivo, P. aeruginosa elastase induced LL-37 degradation in human wound fluid, leading to enhanced bacterial survival. The degradation was blocked by the metalloproteinase inhibitors GM6001 and 1, 10-phenantroline (both of which inhibited P. aeruginosa elastase, P. mirabilis proteinase, and E. faecalis gelatinase), or the inhibitor E64 (which inhibited S. pyogenes cysteine proteinase). Additional experiments demonstrated that dermatan sulphate and disaccharides of the structure [DeltaUA(2S)-GalNAc(4,6S)], or sucroseoctasulphate, in-hibited the degradation of LL-37. The results indicate that proteolytic degradation of LL-37 is a common virulence mechanism and that molecules which block this degradation could have therapeutic potential.
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| 5. |
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| 6. |
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| 7. |
- von Pawel-Rammingen, Ulrich, et al.
(författare)
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Streptococcus pyogenes and phagocytic killing.
- 2002
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 8:10, s. 1043-1044
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Tidskriftsartikel (refereegranskat)
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