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.

Superantigens Subvert the Neutrophil Response To Promote Abscess Formation and Enhance Staphylococcus aureus SurvivalIn Vivo

“…In contrast, S. aureus also secretes superantigens (SAgs) that directly target and activate cells of the adaptive immune system (10,11). The family of SAgs in S. aureus now includes over 20 genetically distinct SAg variants that comprise the staphylococcal enterotoxins (SEs), staphylococcal enterotoxinlike (SEls) toxins, and toxic shock syndrome toxin-1 (TSST-1) (12). These functionally unique exotoxins circumvent antigen presentation by engaging lateral surfaces of major histocompatibility complex class II (MHC-II) molecules (13)(14)(15)(16) and complementarity determining region 2 (CDR2) of the T cell receptor (TCR) ␤-chain variable region (V␤) (17)(18)(19)(20).…”

Detection of Methicillin Resistance and Various Virulence Factors in Staphylococcus aureus Strains Isolated from Nasal Carriers

“…More than 20 SAgs have been identified in S. aureus strains, and a minimum of 80% of clinical strains harbor at least one. SEs cause staphylococcal food poisoning, whereas TSST-1 and ETs are responsible for toxic shock syndrome (TSS) and staphylococcal scalded-skin syndrome (SSSS), respectively (12).…”

CD169+ Macrophages Restrain Systemic Inflammation Induced by Staphylococcus aureus Enterotoxin A Lung Response

“…Thus, there is a disparity in understanding why S. aureus is so common in asymptomatic individuals and, simultaneously, it can trigger a life-threatening inflammatory response. Although the mechanisms of how a commensal colonization can become pathogenic are not clear (38), it has been well established that patients who have colonization of anterior nares with S. aureus and particularly methicillin-resistant S. aureus are more susceptible to hospital-acquired S. aureus infections (39). This suggests that various defense mechanisms must be in place to prevent the spread of the bacteria and limit the effects of the virulence factors; however, these mechanisms may be impaired in immunocompromised individuals in hospital settings.…”