Toxic Shock Syndrome Toxin 1 Contributes to the Arthritogenicity of Staphylococcus aureus

Abdelnour, Arturo; Bremell, Tomas; Tarkowski, Andrzej

doi:10.1093/infdis/170.1.94

Cited by 64 publications

(41 citation statements)

References 30 publications

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“…First, the study was performed using a USA300 strain, which is the predominant S. aureus isolate that causes CA-MRSA infections in the United States. However, prior work found that USA200 S. aureus strains producing toxic shock syndrome toxin-1 (TSST-1) can cause hematogenous and osteomyelitis infections (48,49). Because USA200 strains produce little or no AT because of a stop codon in the AT gene (50), the anti-AT mAb will likely not have an effect in USA200 or in other strains that do not produce AT.…”

Section: Resultsmentioning

confidence: 99%

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

Wang

Cheng²,

Helfer

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Infection is a major complication of implantable medical devices, which provide a scaffold for biofilm formation, thereby reducing susceptibility to antibiotics and complicating treatment. Hematogenous implant-related infections following bacteremia are particularly problematic because they can occur at any time in a previously stable implant. Herein, we developed a model of hematogenous infection in which an orthopedic titanium implant was surgically placed in the legs of mice followed 3 wk later by an i.v. exposure to Staphylococcus aureus. This procedure resulted in a marked propensity for a hematogenous implant-related infection comprised of septic arthritis, osteomyelitis, and biofilm formation on the implants in the surgical legs compared with sham-operated surgical legs without implant placement and with contralateral nonoperated normal legs. Neutralizing human monoclonal antibodies against α-toxin (AT) and clumping factor A (ClfA), especially in combination, inhibited biofilm formation in vitro and the hematogenous implant-related infection in vivo. Our findings suggest that AT and ClfA are pathogenic factors that could be therapeutically targeted against S. aureus hematogenous implant-related infections.hematogenous | implant | Staphylococcus aureus | biofilm | orthopedic

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Section: Resultsmentioning

confidence: 99%

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

Wang

Cheng²,

Helfer

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, microbial superantigens can be arthritogenic because TSST-1 is known to exacerbate bacterial cell wall-induced arthritis in rats [35]. TSST-1 also plays a pivotal role in the development of septic arthritis in mice because the frequency and severity of arthritis are increased in mice injected intravenously with TSST-1-secreting S. aureus [36]. In humans, S. aureus is the causative agent in about 60% of non-gonococcal bacterial arthritis cases [13].…”

Section: Discussionmentioning

confidence: 99%

Induction of CC chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline

Krakauer

1999

Journal of Leukocyte Biology

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We investigated the inflammatory processes that might be associated with the arthrogenic activity of Staphylococcus aureus, the principal causative agent of bacterial arthritis. Human peripheral blood mononuclear cells (PBMC) were stimulated with the staphylococcal toxic shock syndrome toxin-1 (TSST-1) or enterotoxin B (SEB) and the production of chemokines was examined. Both TSST-1 and SEB induced high levels (ng/mL) of MIP-1␣, MIP-1␤, and MCP-1. The induction of these chemokines occurred mostly by direct stimulation of PBMC with staphylococcal exotoxins (SE), without requiring the intervention of IL-1 and TNF-␣. The production of SE-induced chemokines was blocked partially by anti-DR and anti-CD2 antibodies. Cell separation revealed monocytes as the cell source of these chemokines. However, addition of purified T cells amplified the levels of chemokine produced, suggesting that cognate interaction of SE bound on antigen-presenting cells with T cells also contributes to chemokine production. The activation and recruitment of leukocytes by these chemokines may contribute to the pathophysiology of septic arthritis caused by staphylococci in humans through tissue injury and the recruitment of T lymphocytes, perhaps also initiating autoimmune responses. Pentoxifylline, an anti-inflammatory agent, completely inhibited the production of these chemokines. J. Leukoc. Biol. 66: 158-164; 1999.

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“…The infected mice displayed increased levels of inflammatory cytokines, such as tumor necrosis factor and interleukin-6 (IL-6) in serum (7). We have also shown that toxic shock syndrome toxin 1 (TSST-1), a superantigen produced by S. aureus LS-1, contributes to the arthritogenicity of S. aureus (3,5). A series of studies using this model suggested that S. aureus arthritis is a T-cell-dependent and superantigen mediated disease.…”

mentioning

confidence: 97%

Are B Lymphocytes of Importance in SevereStaphylococcus aureusInfections?

et al. 2000

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To investigate the role of B cells in experimental, superantigen-mediated Staphylococcus aureus arthritis and sepsis, we used gene-targeted B-cell-deficient mice. The mice were inoculated intravenously with a toxic shock syndrome toxin 1 (TSST-1)-producing S. aureus strain. The B-cell-deficient and thus agamma-globulinemic mice showed striking similarities to the wild-type control animals with respect to the development of arthritis, the mortality rate, and the rate of bacterial clearance. Surprisingly, we found that the levels of gamma interferon in serum were significantly lower (P < 0.0001) in B-cell-deficient mice than in the controls, possibly due to impaired superantigen presentation and a diminished expression of costimulatory molecules. In contrast, the levels of interleukin-4 (IL-4), IL-6, and IL-10 in serum were equal in both groups. Our findings demonstrate that neither mature B cells nor their products significantly contribute to the course of S. aureus-induced septic arthritis.We have previously described a murine model of hematogenously induced Staphylococcus aureus arthritis and sepsis (7,8). Using this model, approximately 80 to 90% of mice inoculated with S. aureus LS-1 develop clinical arthritis. Immunohistochemical analysis of arthritic joints demonstrated the presence of phagocytes and T cells, predominantly of the CD4 phenotype (4). The infected mice displayed increased levels of inflammatory cytokines, such as tumor necrosis factor and interleukin-6 (IL-6) in serum (7). We have also shown that toxic shock syndrome toxin 1 (TSST-1), a superantigen produced by S. aureus LS-1, contributes to the arthritogenicity of S. aureus (3,5). A series of studies using this model suggested that S. aureus arthritis is a T-cell-dependent and superantigen mediated disease.As to the role of B cells in S. aureus arthritis, we have found that a striking feature in this model is the occurrence of polyclonal B-cell activation with highly increased levels of immunoglobulins and autoantibodies in serum (7). Using X-linked immunodeficiency (xid) mice to investigate the contribution of the B1 subset of B cells to the development of septic arthritis, it was found that this defect provided resistance (21). Since the B1 subset is considered to be of importance in the production of autoantibodies, it was hypothesized that the outcome of the experiment might have been due to this fact.The aim of this study was to investigate if mature B cells, irrespective of their B1 or B2 phenotype, and their products including cytokines, autoantibodies, and antibodies to bacterial constituents would affect the outcome of S. aureus-induced arthritis and sepsis. We report here that a complete absence of mature B cells has no impact on the outcome of these very severe and life-threatening conditions. MATERIALS AND METHODSMice. Gene-targeted B-cell-deficient MT mice (C57BL/6 ϫ 129) (11) were backcrossed to B10.Q (H-2 q ) mice for eight generations and then further intercrossed for two generations to provide homozygous B10.Q mice lacking fu...

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Toxic Shock Syndrome Toxin 1 Contributes to the Arthritogenicity of Staphylococcus aureus

Cited by 64 publications

References 30 publications

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

Induction of CC chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline

Are B Lymphocytes of Importance in SevereStaphylococcus aureusInfections?

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