Staphylococcal superantigens in colonization and disease

Abstract

Superantigens (SAgs) are a family of potent immunostimulatory exotoxins known to be produced by only a few bacterial pathogens, including Staphylococcus aureus. More than 20 distinct SAgs have been characterized from different S. aureus strains and at least 80% of clinical strains harbor at least one SAg gene, although most strains encode many. SAgs have been classically associated with food poisoning and toxic shock syndrome (TSS), for which these toxins are the causative agent. TSS is a potentially fatal disease whereby SAg-mediated activation of T cells results in overproduction of cytokines and results in systemic inflammation and shock. Numerous studies have also shown a possible role for SAgs in other diseases such as Kawasaki disease (KD), atopic dermatitis (AD), and chronic rhinosinusitis (CRS). There is also now a rich understanding of the mechanisms of action of SAgs, as well as their structures and function. However, we have yet to discover what purpose SAgs play in the life cycle of S. aureus, and why such a wide array of these toxins exists. This review will focus on recent developments within the SAg field in terms of the molecular biology of these toxins and their role in both colonization and disease.

Keywords: Staphylococcus aureus; colonization; staphylococcal enterotoxin; superantigen.

Figure 1

Phylogenetic tree of known bacterial SAgs. The unrooted tree was based on the alignment of amino acid sequences constructed with the unweighted pair group method using arithmetic averages (UPGMA) in MacVector 7.2.3. The SAg abbreviations are indicated followed by the relevant accession number. As previously proposed (McCormick et al., 2001), the five main groups of SAgs belonging to the pyrogenic toxin class are indicated. MAM, YPM, and non-Group A streptococcal SAgs are also included in the analysis. The number of times each branch was supported from 1000 bootstraps is shown as a percentage.

Figure 2

Structural overview of the SAg-mediated T cell activation complexes. Ribbon diagram models show (A) conventional T cell activation (Hennecke et al., 2000), and SAg-mediated T cell activation complexes for (B) Group I (e.g., TSST-1) (C) Group II (e.g., SEB) (D) Group III (e.g., SEH) and (E) Group V (e.g., SEl-K). Colors for TCR and MHC class II chains are labeled in Panel (A). The SAg activation complex models were generated by superposition of the TSST-Vβ (Moza et al., 2007) and TSST-MHC class II (Kim et al., 1994) structures, the SEC-Vβ (Fields et al., 1996) and SEB-MHC class II (Jardetzky et al., 1994) structures, the SEH-VαVβ (Saline et al., 2010), SEH-MHC class II β-chain (Petersson et al., 2001), and the SEA-MHC class II α-chain (Petersson et al., 2002) structures, and the SEK-Vβ (Gunther et al., 2007) and SEI-MHC II (Fernandez et al., 2006) structures. The TCR α-chain was modeled for clarity in each case from the conventional complex (Hennecke et al., 2000). The “?” in Panel (E) indicates that there is no current information regarding the presence, or absence, of the generic low-affinity MHC class II binding domain for Group V SAgs.