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

Abstract

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.

Enterotoxigenic Potential of Coagulase-Negative Staphylococci from Ready-to-Eat Food

“…Currently, both enterotoxin groups are represented by 23 toxins [ 9 , 17 ]. These include five basic toxins, SEA, SEB, SEC, SED and SEE [ 7 , 18 ] (new toxins SEG, SEH, SEI, SER, SES, SET, as well as staphylococcal-like toxins such as SElJ, SElK, SElL, SElM, SElN, SElO, SElP, SElQ, SElU, SElU2, SElV, SElX [ 19 , 20 , 21 , 22 , 23 , 24 ]. The toxins with proven vomit-inducing ability include SEA to SEI, SER, SES, SEQ and SET.…”

Basis of Virulence in Enterotoxin-Mediated Staphylococcal Food Poisoning

“…The expression of SFP-associated SEH, which is produced predominantly in the late exponential phase of bacterial growth (Sakai et al, 2008 ; Lis et al, 2012 ), was recently shown to be positively regulated by Rot, via direct binding to the seh promoter (Sato'o et al, 2015 ), σB (Kusch et al, 2011 ), several Sar homologs, and SaeR (Sato'o et al, 2015 ). Moreover, SaeRS appears to have a positive impact on SE l X (Langley et al, 2017 ) and TSST-1 (Baroja et al, 2016 ) expression. In contrast, the production of enterotoxins encoded in the egc operon (SEG, SEI, SEM, SEN, SEO, and SE l U) is highest in the earliest stages of exponential growth (Grumann et al, 2008 ) and dependent on σB (Kusch et al, 2011 ).…”

“…Recently, it was discovered that SE l X has a unique sialic acid-binding motif. This motif allows SE l X to interact with adhesion molecules on neutrophils involved in immune recognition and cell activation (Langley et al, 2017 ; Tuffs et al, 2017 ). Importantly, the ability of SE l X to bind neutrophils, which are considered the first line of defense against S. aureus (Spaan et al, 2013 ), was crucial for disease progression in a rabbit model of necrotizing pneumonia.…”

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

“…In contrast, in a renal abscess model, S. aureus JSNZ caused a more severe disease than S. aureus Newman [ 171 ]. In a subcutaneous infection model, S. aureus JSNZ showed a stronger upregulation of saeR transcripts (in relation to in vitro cultures) than S. aureus Newman [ 174 ], which might hint at a different virulence factor regulation in the mouse.…”