| 1. |
- Frick, Julia S, et al.
(författare)
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Identification of commensal bacterial strains that modulate Yersinia enterocolitica and dextran sodium sulfate-induced inflammatory responses : implications for the development of probiotics.
- 2007
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 75:7, s. 3490-7
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Tidskriftsartikel (refereegranskat)abstract
- An increasing body of evidence suggests that probiotic bacteria are effective in the treatment of enteric infections, although the molecular basis of this activity remains elusive. To identify putative probiotics, we tested commensal bacteria in terms of their toxicity, invasiveness, inhibition of Yersinia-induced inflammation in vitro and in vivo, and modulation of dextran sodium sulfate (DSS)-induced colitis in mice. The commensal bacteria Escherichia coli, Bifidobacterium adolescentis, Bacteroides vulgatus, Bacteroides distasonis, and Streptococcus salivarius were screened for adhesion to, invasion of, and toxicity for host epithelial cells (EC), and the strains were tested for their ability to inhibit Y. enterocolitica-induced NF-kappaB activation. Additionally, B. adolescentis was administered to mice orally infected with Y. enterocolitica and to mice with mucosae impaired by DSS treatment. None of the commensal bacteria tested was toxic for or invaded the EC. B. adolescentis, B. distasonis, B. vulgatus, and S. salivarius inhibited the Y. enterocolitica-induced NF-kappaB activation and interleukin-8 production in EC. In line with these findings, B. adolescentis-fed mice had significantly lower results for mean pathogen burden in the visceral organs, intestinal tumor necrosis factor alpha mRNA expression, and loss of body weight upon oral infection with Y. enterocolitica. In addition, the administration of B. adolescentis decelerated inflammation upon DSS treatment in mice. We suggest that our approach might help to identify new probiotics to be used for the treatment of inflammatory and infectious gastrointestinal disorders.
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| 2. |
- Mühlenkamp, Melanie C., et al.
(författare)
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Vitronectin Binds to a Specific Stretch within the Head Region of Yersinia Adhesin A and Thereby Modulates Yersinia enterocolitica Host Interaction
- 2017
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 9:1, s. 33-51
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Tidskriftsartikel (refereegranskat)abstract
- Complement resistance is an important virulence trait of Yersinia enterocolitica (Ye). The predominant virulence factor expressed by Ye is Yersinia adhesin A (YadA), which enables bacterial attachment to host cells and extracellular matrix and additionally allows the acquisition of soluble serum factors. The serum glycoprotein vitronectin (Vn) acts as an inhibitory regulator of the terminal complement complex by inhibiting the lytic pore formation. Here, we show YadA-mediated direct interaction of Ye with Vn and investigated the role of this Vn binding during mouse infection in vivo. Using different Yersinia strains, we identified a short stretch in the YadA head domain of Ye O:9 E40, similar to the ‘uptake region' of Y. pseudotuberculosis YPIII YadA, as crucial for efficient Vn binding. Using recombinant fragments of Vn, we found the C-terminal part of Vn, including heparin-binding domain 3, to be responsible for binding to YadA. Moreover, we found that Vn bound to the bacterial surface is still functionally active and thus inhibits C5b-9 formation. In a mouse infection model, we demonstrate that Vn reduces complement-mediated killing of Ye O:9 E40 and, thus, improved bacterial survival. Taken together, these findings show that YadA-mediated Vn binding influences Ye pathogenesis.
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| 3. |
- Riess, Tanja, et al.
(författare)
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Bartonella adhesin A mediates a proangiogenic host cell response
- 2004
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 200:10, s. 1267-1278
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Tidskriftsartikel (refereegranskat)abstract
- Bartonella henselae causes vasculoproliferative disorders in humans. We identified a nonfimbrial adhesin of B. henselae designated as Bartonella adhesin A (BadA). BadA is a 340-kD outer membrane protein encoded by the 9.3-kb badA gene. It has a modular structure and contains domains homologous to the Yersinia enterocolitica nonfimbrial adhesin (Yersinia adhesin A). Expression of BadA was restored in a BadA-deficient transposon mutant by complementation in trans. BadA mediates the binding of B. henselae to extracellular matrix proteins and to endothelial cells, possibly via β1 integrins, but prevents phagocytosis. Expression of BadA is crucial for activation of hypoxia-inducible factor 1 in host cells by B. henselae and secretion of proangiogenic cytokines (e.g., vascular endothelial growth factor). BadA is immunodominant in B. henselae–infected patients and rodents, indicating that it is expressed during Bartonella infections. Our results suggest that BadA, the largest characterized bacterial protein thus far, is a major pathogenicity factor of B. henselae with a potential role in the induction of vasculoproliferative disorders.
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| 4. |
- Wiedig, Carolin A, et al.
(författare)
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Induction of CD8+ T cell responses by Yersinia vaccine carrier strains.
- 2005
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Ingår i: Vaccine. - 0264-410X. ; 23:42, s. 4984-98
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Tidskriftsartikel (refereegranskat)abstract
- Yersinia enterocolitica employs a type III secretion system (TTSS) to target virulence factors (e.g. YopE) into the cytosol of the host cells. We utilized the TTSS to introduce a recombinant antigen directly into the cytosol of host cells and to investigate the potential of Y. enterocolitica and Y. pseudotuberculosis as live carrier for vaccines. The model antigen ovalbumin (Ova) was fused to defined secretion or translocation domains of the Yersinia effector protein YopE and introduced into attenuated mutant strains of Y. enterocolitica and Y. pseudotuberculosis. In vitro experiments showed secretion and translocation of YopE-Ova hybrid proteins into host cells. To investigate the resulting immune responses, mice expressing transgenic Ova-specific T cell receptors were used. Both Y. enterocolitica and Y. pseudotuberculosis mutants induced efficaciously Ova-specific CD8+ T cell responses. The translocation domain of YopE was required for induction of CD8+ T cell responses in vivo, but not for T cell responses induced in vitro. The in vivo frequency of Ova-specific splenic T cells was up to six-fold higher in mice immunized with YopE-Ova-translocating Y. enterocolitica/Y. pseudotuberculosis mutants than in control mice. The Ova-specific T cells were shown to produce high amounts of IFN-gamma. We did not observe significant Ova-specific CD4+ T cell or antibody responses upon vaccination with either of the strains. In conclusion, Yersinia live carrier vaccine strains are suitable to target antigens into the MHC class I pathway and stimulate CD8+ T cell responses and thus, might be useful in vaccine approaches against intracellular pathogens.
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