Staphylococcal Toxins and Protein A Differentially Induce Cytotoxicity and Release of Tumor Necrosis Factor–α From Human Keratinocytes

It has been proposed that toxins and other bacterial protein products of Staphylococcus aureus can act as triggers or persistence factors in several inflammatory skin diseases. In this study, we examined the S. aureus isolates from the skin of patients with atopic dermatitis and psoriasis. We found that the bacterial isolates from these patients exihibited either characteristics superantigenic toxins or thermolabile toxins believed to be staphylococal α-toxin. All of these staphylococcal strains also secreted extracellular staphylococcal protein A. We found significant differences in the action of these toxins on human keratinocytes and keratinocyte cell lines. The superantigenic toxins toxic shock syndrome toxin–1, staphylococcal enterotoxins A and B, and exfoliative toxin–A. as well as staphylococcal protein A, did not induce significant cytotoxic damage in the keratinocyte cell line HaCaT, whereas the staphylococcal α-toxin produced profound cytotoxicity. Keratinocyte cytotoxity induced by staphylococcal α-toxin was time and concentration dependent and demonstrated the morphologic and functional characteristics of necrosis, not apoptosis. Addition of α-toxin to keratinocytes simultaneously induced cell lysis and tumor necrosis factor–α release into the medium within 30 min; apparently, it was constitutive tumor necrosis factor–α. On the other hand, superantigenic toxins and, in particular, protein A showed stimulation of tumor necrosis factor-α secretion in keratinocytes and release of this cytokine after 6–12h of incubation. Thus, staphylococcal protein A, α-toxin, and superantigenic toxins found in S. aureus isolates from patients with psoriasis and atopic dermatitis can produce direct pro-inflammatory effects on kerationcytes through the release of tumor necrosis factor–α. We propose that these effects may be relevant to the induction and persistence of lesions in these two disease

Nobel laureate Ilya I. Metchnikoff (1845-1916). Life story and scientific heritage

A century of science after I. Metchnikoff’s death demonstrated the truth in many of his views and judgments in the field of immunology, pathology, bacteriology, zoology and comparative embryology. Today Metchnikoff is deservedly called the father of the theory of cellular immunity, and also a harbinger of the theo­ry of natural immunity. His work in the field of lactic acid bacteria formed the basis for an entire industry of probiotics. Metchnikoff’s doctrine of the possibility of extending human life is still relevant. This publication is one more attempt to tie the biography of the scientist with his creative legacy and his contribution in the world treasury of biological science

Staphylococcus aureus Isolates from Patients with Kawasaki Disease Express High Levels of Protein A

Kawasaki disease (KD) is an acute vasculitis of young children that can be complicated by coronary artery abnormalities. Recent findings suggest that a superantigen(s) may play an important role in stimulating the immune activation associated with the disease, although the origin of this superantigen(s) is unclear. Staphylococcus aureus, isolated from the rectum or pharynx of patients with KD, secretes toxic shock syndrome toxin 1 (TSST-1). The KD isolates express low levels of other exoproteins compared to isolates from patients with toxic shock syndrome (TSS). Thus, it was previously suggested that the KD isolates may be defective in the global regulatory locus agr (for accessory gene regulator), which positively regulates these factors (D. Y. M. Leung et al., Lancet 342:1385–1388, 1993). Here we describe another characteristic of KD isolates. When considered collectively, the KD isolates were found to express higher levels of staphylococcal protein A than the TSS isolates, another characteristic of an agr-defective phenotype. This correlated with a higher level of spa mRNA in these isolates. In contrast, the KD and TSS isolates expressed comparable levels of TSST-1, consistent with previous findings (D. Y. M. Leung et al., Lancet 342:1385–1388, 1993). Analysis of RNAIII transcript levels and nucleotide sequence analysis of the RNAIII-coding region suggested that the KD isolates are not defective in RNAIII, the effector molecule of the agr regulatory system. However, induction of RNAIII transcription in the KD isolates did not result in a dramatic decrease in the amount of spa mRNA, as has been reported for other strains (F. Vandenesch, J. Kornblum, and R. P. Novick, J. Bacteriol. 173:6313–6320, 1991)