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.

金黄色葡萄球菌是一种机会致病菌，可产生许多毒力因子。其中的两个主要家族是葡萄球菌超抗原（SAgs）和葡萄球菌超抗原样（SSL）外蛋白。前者是诱导T细胞Vβ特异性活化的免疫调节毒素，而后者是干扰多种先天免疫防御的免疫逃避分子。最近已经建立了葡萄球菌肠毒素样X（SElX）的超抗原性。现在，我们揭示SElX还具有SSL的功能特征。SElX的一个区域与SSL子家族中的唾液酸-乳糖胺（sLacNac）特异性结合位点显示出高度同源性。通过分析SElX与含sLacNac的聚糖的相互作用，我们表明SElX具有与SSL相同的特异性和宿主细胞结合范围。该保守区域中关键氨基酸的突变会影响SElX与髓样来源细胞结合的能力，并显着降低其保护能力小号。全血杀死（WBK）分析中破坏的金黄色葡萄球菌。像SSL一样，SElX在感染过程中早期被上调，并且受S的控制。金黄色素外毒素表达（Sae）两成分基因调控系统。另外，与含有sLacNac的四糖唾液酸路易斯X（sLeX）复合的SElX的结构揭示了SElX是独特的单结构域SAg。总之，SElX是一个“类似SSL”的SAg。