Abstract
Staphylococcal Enterotoxins (SEs) are superantigens (SAg) originally produced by S. aureus, but their presence in coagulase negative staphylococci (CNS) has long been suspected. This study aims to better characterize a novel C-like enterotoxin expressed by clinical S. epidermidis strains, called SECepi. We isolated and characterized SECepi for its molecular and functional properties. The toxin was structurally modeled according to its significant similarity with S. aureus SEC3. Most of SEC amino acid residues important for the formation of the trimolecular Major Histocompatibility Complex II MHCII–SEC–T Cell Receptor TCR complex are conserved in SECepi. The functional properties of SECepi were estimated after cloning, expression in E. coli, and purification. The recombinant SECepi toxin exhibits biological characteristics of a SAg including stimulation of human T-cell mitogenicity, inducing and releasing high cytokines levels: IL-2, -4, -6, -8, -10, IFN-γ, TNF-α and GM-CSF at a dose as low as 3.7 pM. Compared to SECaureus, the production of pro-sepsis cytokine IL-6 is significantly higher with SECepi-activated lymphocytes. Furthermore, SECepi is stable to heat, pepsin or trypsin hydrolysis. The SECepi superantigen produced by CNS is functionally very close to that of S. aureus, possibly inducing a systemic inflammatory response at least comparable to that of SECaureus, and may account for S. epidermidis pathogenicity.
Highlights
Staphylococcal superantigens (SAgs) represent a large family of at least 23 members in S. aureus that includes toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxins (SEs), and SE-like (SEl) where emetic activities are lacking, not yet confirmed or whose roles in diseases remain under investigation [1,2,3,4]
Homology analysis of the deduced amino acids sequences of the amplified sec genes revealed that SECepi were 100% conserved among both two isolates, while analysis of the generated dendrogram issued from the MALDI-TOF spectrum of the 22 strains shows that both the two sec positive isolates strains do not aggregate in a single cluster (Figure 1)
It was reported that acquisition of SE(s) gene(s) by coagulase negative staphylococci (CNS) strains would be a rare or isolated event [26], the present study revealed that the SEs genes exist in a food poisoning isolate [1], and in CNS isolates from cases of human infectious diseases
Summary
Staphylococcal superantigens (SAgs) represent a large family of at least 23 members in S. aureus that includes toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxins (SEs), and SE-like (SEl) where emetic activities are lacking, not yet confirmed or whose roles in diseases remain under investigation [1,2,3,4]. SEs are common causes of food poisoning but were involved in acute atopic eczema [5], urticaria [6] and rheumatoid arthritis [7] Their involvement in lethal sepsis, infectious endocarditis, acute kidney injury and necrotizing pneumonia are demonstrated in animal models [8,9]. These toxins are active on gastrointestinal and endothelial cells, and function as superantigens that stimulate a non-specific but vigorous proliferation of T-cells bearing. Toxins 2018, 10, 139 certain T Cell Receptor Vβ-chain variable regions [2,10] This hyperstimulation occurs through the binding of enterotoxin to the α-helical regions of the Major Histocompatibility Complex class. Conventional antigens stimulate 0.01% of T-cells, while SAgs can stimulate
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