Clostridium difficile infection (CDI) is a common and debilitating nosocomial infection with high morbidity and mortality. C. difficile mediates diarrhea and colitis by releasing two toxins, toxin A and toxin B. Since both toxins stimulate proinflammatory signaling pathways in human colonocytes and both are involved in the pathophysiology of CDI, neutralization of toxin A and B activities may r...

Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1) is involved in the pathogenesis of toxic shock syndrome and perhaps other staphylococcal diseases. Recently, the C-terminal part of the TSST-1 toxin has been shown to be responsible for mitogenic activity in animal models. We studied the role of the C-terminal structural unit of TSST-1 with regard to proliferation, cytokine release (tu...

background: cigarette smoking has been linked with the suppression of immune responses and increased susceptibility to numerous infections in humans. tetanus is also a major public health problem in many countries. the aim of the present study was to evaluate the serum levels of anti-tetanus toxin antibodies in c igarette smoking and healthy non-smoking people .   materials and methods: a total...

  Background: Cigarette smoking has been linked with the suppression of immune responses and increased susceptibility to numerous infections in humans. Tetanus is also a major public health problem in many countries. The aim of the present study was to evaluate the serum levels of anti-tetanus toxin antibodies in c igarette smoking and healthy non-smoking people .   Materials and M...

Clostridium difficile toxin A is associated with enterocolitis in animals and humans. However, the mechanisms of its secretory and damaging effects are not totally understood. In this work, we examined the intestinal secretion of electrolytes and water caused by supernatants from macrophages stimulated with toxin A in rabbit ileal mucosa mounted in Ussing chambers. We also investigated the mech...

MEDI4893 is a neutralizing human monoclonal antibody that targets alpha toxin (AT), and is currently undergoing evaluation in the field of Staphylococcus aureusmediated diseases. We have solved the crystal structure of MEDI4893 Fab bound to monomeric AT at a resolution of 2.56 Å, and further characterized its epitope using various engineered AT variants. We have found that MEDI4893 recognizes a...

Clostridium perfringens alpha-toxin induces the generation of superoxide anion (O2(-)) via production of 1,2-diacylglycerol (DG) in rabbit neutrophils. The mechanism of the generation, however, remains poorly understood. Here we report a novel mechanism for the toxin-induced production of O2(-) in rabbit neutrophils. Treatment of the cells with the toxin resulted in tyrosine phosphorylation of ...

background: periodontitis and rheumatoid arthritis (ra) share a number of clinical and pathologic features, one of which is the presence of the tumor necrosis factor alpha (tnf-α)-induced bone resorption that is involved in the pathogenesis of both. objectives: to investigate the effect of tnf-α blockade on periodontal conditions in patients with active ra. method: the periodontal statuses of 3...

Recombinant Bacillus subtilis endospores have been used to vaccinate against tetanus and anthrax. In this work, we have developed spores that could be used to vaccinate against Clostridium perfringens alpha toxin and that could be used to protect against gas gangrene in humans and necrotic enteritis in poultry. The primary active agent in both cases is alpha toxin. A carboxy-terminal segment of...