Publications (80) View all
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Article: The influence of SaeRS and σ(B) on the expression of superantigens in different Staphylococcus aureus isolates.
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ABSTRACT: Staphylococcus aureus is a major human pathogen. Superantigens (SAg) are important virulence factors in S. aureus, but the regulation of SAg gene expression is largely unknown. Using 2 sequenced S. aureus strains (COL and Newman) and 4 clinical isolates, regulation of gene expression was investigated in more detail for 12 SAgs. The SAg-encoding genes were expressed in a growth phase-dependent manner: while the egc operon was mainly transcribed at low optical densities, the transcription of seb was induced at high optical densities. The transcript levels of sea, sek, seq, sep, and tst-1 did not change significantly during growth. The T cell-mitogenic activity of supernatants correlated with the transcription data. SaeRS and σ(B) strongly influenced SAg gene transcription. σ(B) activated transcription of seh, tst-1, and of the egc operon. A possible σ(B)-dependent promoter was identified in front of the egc operon. In contrast, a loss of σ(B) enhanced the transcript level of seb, suggesting an indirect effect of the alternative sigma factor on the transcription of this gene. Transcriptional studies of an saeS mutant showed that the two-component system only activates transcription of seb. The influence of σ(B) and SaeRS on the expression of SAg genes was validated by T cell proliferation assays. For sigB mutants in different strains, different effects on the T cell-mitogenic potential were observed depending on the SAg gene repertoire of the isolates.International journal of medical microbiology: IJMM 04/2011; 301(6):488-99. · 2.80 Impact Factor -
Article: Chances and perspectives of the plasma medicine by use of Tissue Tolerable Plasma (TTP)
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ABSTRACT: On the basis of our current knowledge about the physical properties and biological effects of low temperature plasmas the possibilities and prospects of plasma medicine are discussed in an interdisciplinary dialogue in order to generate hypotheses for further basic and applied research.The following possibilities are seemed feasible for the medical application of low-temperature plasmas: * Prevention and treatment of diseases (chronic wounds, skin and mucosal infectious diseases, localized tumors, keloid formation, promotion of angiogenesis, tissue ablation, hemostasis) * Inhibition of biofilm formation by surface treatment and by direct action on biofilms * Promotion of incorporation of implants into viable tissue by changing the surface (hydrophobicity, plasma steered application of antimicrobial active layers with drug delivery function) * Promotion of improved penetration of topically applied drugs with therapeutic outcome * Employment for veterinary indications * Improved cleaning performance in the treatment process of medical devices by surface modification.GMS Krankenhaushygiene Interdisziplinär. 01/2009; -
Article: Antibody responses in furunculosis patients vaccinated with autologous formalin-killed Staphylococcus aureus.
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ABSTRACT: Autologous vaccines (short: autovaccines) have been used since the beginning of the 20th century to treat chronic staphylococcal infections, but their mechanisms of action are still obscure. This prospective pilot study involved four patients with furunculosis who were vaccinated with autologous formalin-killed Staphylococcus aureus cells. Vaccines were individually prepared from the infecting S. aureus strain and repeatedly injected subcutaneously in increasing doses over several months. We characterized the virulence gene repertoire and spa genotype of the infecting and colonising S. aureus strains. Serum antibody responses to secreted and surface-bound bacterial antigens were determined by two-dimensional immunoblotting and flow-cytometry based assays (Luminex). All patients reported clinical improvement. Molecular characterization showed that all strains isolated from one patient over time belonged to the same S. aureus clone. Already before treatment, there was robust antibody binding to a broad range of staphylococcal antigens. Autovaccination moderately boosted the IgG response to extracellular antigens in two patients, while the antibody response of the other two patients was not affected. Similarly, vaccination moderately enhanced the antibody response against some staphylococcal surface proteins, e.g. ClfA, ClfB, SdrD and SdrE. In summary, autovaccination only slightly boosted the pre-existing serum antibody response, predominantly to bacterial surface antigens.European Journal of Clinical Microbiology 06/2011; 30(6):707-17. · 2.86 Impact Factor -
Article: Expression of staphylococcal superantigens during nasal colonization is not sufficient to induce a systemic neutralizing antibody response in humans.
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ABSTRACT: Staphylococcus aureus carriers have high-titer serum antibodies against non-enterotoxin gene cluster (egc) superantigens, whereas they lack anti-egc antibodies, suggesting different superantigen expression profiles in vivo. We measured the superantigen transcripts in S. aureus directly isolated from the nose of persistent carriers and correlated them with the superantigen-neutralizing antibody response. While neutralizing serum antibodies against the staphylococcal enterotoxins A and C (SEA and SEC) were found in carriers, antibodies against the egc-encoded staphylococcal enterotoxin-like toxin O (SElO) were rare. Surprisingly, the transcription of selo was comparable to sea and sec during nasal colonization. Thus, egc superantigens are transcribed during nasal colonization, but this is not sufficient to induce a serum antibody response.European Journal of Clinical Microbiology 05/2011; 31(3):251-6. · 2.86 Impact Factor -
Article: The impact of the CTLA-4/CD28 axis on the processes of Joint Inflammation in Rheumatoid Arthritis.
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ABSTRACT: OBJECTIVE: The importance of the co-stimulatory molecules CD28 and CTLA-4 in the pathological mechanism of Rheumatoid Arthritis (RA) is well documented by genetic associations and the successful clinical application of CTLA-4Ig for the treatment of RA. Here we have investigated the role of the CD28/CTLA-4 axis for the local application of CTLA-4Ig in the synovial fluid (SF) of RA patients. METHODS: We analyzed the expression of pro- and anti-inflammatory cytokines by qPCR in FACS-sorted CTLA-4 positive and negative T helper cells from peripheral blood and SF from RA patients ex vivo as well as in T helper cells in vitro after blockade of CTLA-4 by anti-CTLA-4-Fab-fragments or the blockade of B7 (CD80/CD86)-molecules by CTLA-4Ig. RESULTS: CTLA-4(+) T helper cells were unambiguously present in the SF of all RA patients examined and these expressed increased amounts of IFNγ, IL-17 but also IL-10. Furthermore, the selective blockade of CTLA-4 in T helper cells from the SF in vitro led to increased levels of IFNγ, IL-2 and IL-17. In contrast, the concomitant blockade of CD28 and CTLA-4 in T helper cells from SF of RA patients by CTLA-4Ig in vitro resulted in the reduction of the pro-inflammatory cytokines IFNγ and IL-2 accompanied by increased amounts of the anti-inflammatory cytokines IL-10 and TGFβ. CONCLUSION: Our ex vivo and in vitro results demonstrate that the CD28/CTLA-4 axis constitutes a drug target not only for the systemic but potentially also for the local application of the co-stimulation blocking agent CTLA-4Ig for the treatment of RA. © 2012 American College of Rheumatology.Arthritis & Rheumatism 10/2012; · 7.87 Impact Factor
