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

Ries J. Langley, Yi Tian Ting, Fiona Clow, Paul G. Young, Fiona J. Radcliff, Jeong Min Choi, Richard P. Sequeira, Silva Holtfreter, Heather Baker, John D. Fraser

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Article numbere1006549
Number of pages29
JournalPLoS Pathogens
Volume13
Issue number9
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • Staphylococcus aureus
  • binding analysis
  • major histocompatability complex
  • cell binding
  • mouse models
  • blood
  • Staphylococcus
  • sequence motif analysis

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