Bacterial superantigens and superantigen-like toxins

Langley, Ries J.; Fraser, John D.; Proft, Thomas

doi:10.1016/b978-0-12-800188-2.00032-x

Cited by 14 publications

(23 citation statements)

References 411 publications

(484 reference statements)

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“…Glycan binding did not appear to influence the superantigen activity of SElX however, since both SElX and SElX-T130A/R141A displayed an equivalent capacity to stimulate the proliferation of PBMCs ( Fig 7B ). Both SElX and its glycan-binding site mutant displayed ½ maximal PBMC stimulation at approximately 10ng/ml, whereas TSST-1 had a more typical superantigenic potential with its ½ maximal stimulation in the low pg/ml range [ 21 ].…”

Section: Resultsmentioning

confidence: 99%

“…Yet this did not correlate with its ability to stimulate the proliferation of PBMCs since SElX-T130A/R141A displayed an equivalent activity to SElX. The superantigenic capacity of SElX however, was less potent than that of the typical SAgs [ 21 ]. These observations suggest a different mode of action for the T cell stimulation activity observed for SELX.…”

Section: Discussionmentioning

confidence: 99%

“…It is the ensuing ‘cytokine storm’ that is responsible for the symptoms of shock and organ failure that result. Currently there are 25 known staphylococcal and 11 streptococcal SAgs many of which have been crystallized alone or in complex with MHC class II, TcR, or both [ 21 , 22 ]. These SAgs share a common fold consisting of two highly stable domains, the N-terminal OB-fold domain and the C-terminal β-grasp domain, that are separated by a long, partially solvent-accessible central α-helix [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors

et al. 2017

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Staphylococcus aureus is an opportunistic pathogen that produces many virulence factors. Two major families of which are the staphylococcal superantigens (SAgs) and the Staphylococcal Superantigen-Like (SSL) exoproteins. The former are immunomodulatory toxins that induce a Vβ-specific activation of T cells, while the latter are immune evasion molecules that interfere with a wide range of innate immune defences. The superantigenic properties of Staphylococcal enterotoxin-like X (SElX) have recently been established. We now reveal that SElX also possesses functional characteristics of the SSLs. A region of SElX displays high homology to the sialyl-lactosamine (sLacNac)-specific binding site present in a sub-family of SSLs. By analysing the interaction of SElX with sLacNac-containing glycans we show that SElX has an equivalent specificity and host cell binding range to the SSLs. Mutation of key amino acids in this conserved region affects the ability of SElX to bind to cells of myeloid origin and significantly reduces its ability to protect S. aureus from destruction in a whole blood killing (WBK) assay. Like the SSLs, SElX is up-regulated early during infection and is under the control of the S. aureus exotoxin expression (Sae) two component gene regulatory system. Additionally, the structure of SElX in complex with the sLacNac-containing tetrasaccharide sialyl Lewis X (sLeX) reveals that SElX is a unique single-domain SAg. In summary, SElX is an ‘SSL-like’ SAg.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors

et al. 2017

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“…Which Vβ subfamilies are stimulated, again depends on the SAg and can even vary between different variants [92]. The following human Vβ-specificity was found for variants SEC 1-3 : C 1 : 3.2, 6.4, 6.9, 12, 15.1; C 2 : 12, 13, 14, 15, 17, 20; and C 3 : 5.1, 12 [123][124][125]. SEC bovine has been shown to specifically activate the Vβ repertoire of cattle [126].…”

Section: Superantigenic Activity Of Secmentioning

confidence: 99%

Staphylococcal Enterotoxin C—An Update on SEC Variants, Their Structure and Properties, and Their Role in Foodborne Intoxications

Etter

Schelin

Schuppler

et al. 2020

Toxins

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Staphylococcal enterotoxins are the most common cause of foodborne intoxications (staphylococcal food poisoning) and cause a wide range of diseases. With at least six variants staphylococcal enterotoxin C (SEC) stands out as particularly diverse amongst the 25 known staphylococcal enterotoxins. Some variants present unique and even host-specific features. Here, we review the role of SEC in human and animal health with a particular focus on its role as a causative agent for foodborne intoxications. We highlight structural features unique to SEC and its variants, particularly, the emetic and superantigen activity, as well as the roles of SEC in mastitis and in dairy products. Information about the genetic organization as well as regulatory mechanisms including the accessory gene regulator and food-related stressors are provided.

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“…The term “superantigen” commonly describes the S. aureus SEs and toxic shock syndrome toxin-1 (TSST-1), while related streptococcal pyrogenic exotoxins (SPEs), also known as superantigens, are produced by Streptococcus pyogenes . Superantigen was first used in late 1980s literature to describe microbial proteins that activate a large population of specific T-cells at very minute (picogram) concentrations ( 62 , 63 ). Typical “conventional” antigens stimulate far fewer T-cells at higher concentrations.…”

Section: The Staphylococcal Enterotoxinsmentioning

confidence: 99%

Staphylococcal Superantigens Spark Host-Mediated Danger Signals

2016

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Staphylococcal enterotoxin B (SEB) of Staphylococcus aureus, and related superantigenic toxins produced by myriad microbes, are potent stimulators of the immune system causing a variety of human diseases from transient food poisoning to lethal toxic shock. These protein toxins bind directly to specific Vβ regions of T-cell receptors (TCR) and major histocompatibility complex (MHC) class II on antigen-presenting cells, resulting in hyperactivation of T lymphocytes and monocytes/macrophages. Activated host cells produce excessive amounts of proinflammatory cytokines and chemokines, especially tumor necrosis factor α, interleukin 1 (IL-1), IL-2, interferon γ (IFNγ), and macrophage chemoattractant protein 1 causing clinical symptoms of fever, hypotension, and shock. Because of superantigen-induced T cells skewed toward TH1 helper cells, and the induction of proinflammatory cytokines, superantigens can exacerbate autoimmune diseases. Upon TCR/MHC ligation, pathways induced by superantigens include the mitogen-activated protein kinase cascades and cytokine receptor signaling, resulting in activation of NFκB and the phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Various mouse models exist to study SEB-induced shock including those with potentiating agents, transgenic mice and an “SEB-only” model. However, therapeutics to treat toxic shock remain elusive as host response genes central to pathogenesis of superantigens have only been identified recently. Gene profiling of a murine model for SEB-induced shock reveals novel molecules upregulated in multiple organs not previously associated with SEB-induced responses. The pivotal genes include intracellular DNA/RNA sensors, apoptosis/DNA damage-related molecules, immunoproteasome components, as well as antiviral and IFN-stimulated genes. The host-wide induction of these, and other, antimicrobial defense genes provide evidence that SEB elicits danger signals resulting in multi-organ damage and toxic shock. Ultimately, these discoveries might lead to novel therapeutics for various superantigen-based diseases.

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Bacterial superantigens and superantigen-like toxins

Cited by 14 publications

References 411 publications

Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors

Staphylococcal enterotoxin-like X (SElX) is a unique superantigen with functional features of two major families of staphylococcal virulence factors

Staphylococcal Enterotoxin C—An Update on SEC Variants, Their Structure and Properties, and Their Role in Foodborne Intoxications

Staphylococcal Superantigens Spark Host-Mediated Danger Signals

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