Streptococcal Toxic Shock Syndrome

Superantigens (SAgs) are the most powerful T-cell mitogens ever discovered. By simultaneously binding to the major histocompatibility class II molecule on the surface of antigen-presenting cells and to the T cell receptor (TcR) on T cells, SAgs trigger a strong oligoclonal expansion of T cells and the release of massive amounts of proinflammatory cytokines. Thus far, bacterial SAgs have been found in Streptococcus pyogenes (Group A Streptococcus), Group C Streptococcus, Group G Streptococcus, several species of Staphylococcus, Yersinia pseudotuberculosis, and Mycoplasma arthritidis. The streptococcal and staphylococcal SAgs form a large family of structurally related toxins that appear to have a common ancestor. This chapter gives a detailed overview of the structure, biological function, and clinical associations of bacterial SAgs. In addition, we discuss the staphylococcal superantigen-like (SSL) proteins, a novel toxin family of Staphylococcus aureus that are structurally related to SAgs, but target different parts of the innate immune response.

Streptococcus suis is an important zoonotic pathogen worldwide and is responsible for disease in swine and humans. In the present study, we identified and characterised a surface-associated peptidase (abpb, amylase-binding protein B) in Streptococcus suis serotype 2 (S. suis 2) that has high hydrolytic activity towards H-Arg-pNa, with maximum activity at pH 7.0. Stimulation of RAW 264.7 macrophages with purified recombinant abpb protein triggered the release of pro-inflammatory cytokines. An abpb-deficient mutant ΔAbpb was constructed by homologous recombination to determine the role of abpb in S. suis 2. The mutant ΔAbpb showed decreased adherence to Hep-2 cells and attenuated virulence in a mouse model compared to the wild type strains. The results of the infection showed impaired bacterial growth in vivo and poor colonisation of the organs. In a protection assay, the recombinant abpb provided excellent protection against a lethal challenge of S. suis 2. Together, these findings suggest that abpb contributes to the pathogenicity of S. suis 2 and may be another target for S. suis prevention and control.

Superantigens (SAgs) include a class of certain bacterial and viral proteins exhibiting highly potent lymphocyte-transforming (mitogenic) activity towards human and or other mammalian T lymphocytes. Unlike conventional antigens, SAgs bind to certain regions of major histocompatibility complex (MHC) class II molecules of antigen-presenting cells (APCs) outside the classical antigen-binding groove and concomitantly bind in their native form to T cells at specific motifs of the variable region of the β chain (Vβ) of the T cell receptor (TcR). This interaction triggers the activation (proliferation) of the targeted T lymphocytes and leads to the in vivo or in vitro release of high amounts of various cytokines and other effectors by immune cells. Each SAg interacts specifically with a characteristic set of Vβ motifs. The review summarizes our current knowledge on S. aureus and S. pyogenes superantigen proteins. The repertoire of the staphylococcal and streptococcal SAgs comprises 24 and 8 proteins, respectively. The staphylococcal SAgs include (i) the classical enterotoxins A, B, C (and antigenic variants), D, E, and the recently discovered enterotoxins G to Q, (ii) toxic shock syndrome toxin-1, (iii) exfoliatins A and B. The streptococcal SAgs include the classical pyrogenic exotoxins A and C and the newly identified pyrogenic toxins, G, H, I, J, SMEZ, and SSA. The structural and genomic aspects of these toxins and their molecular relatedness are described as well as the available 3-D crystal structure of some of them and that of certain of their complexes with MHC class II molecules and the TcR, respectively. The pathophysiological properties and clinical disorders related to these SAgs are reviewed.