Langley, Ries JTing, Yi TianClow, FionaYoung, Paul GRadcliff, Fiona JChoi, Jeong MinSequeira, Richard PHoltfreter, SilvaBaker, HeatherFraser, John DPrince, Alice2025-03-112025-03-112017-09(2017). PLoS Pathogens, 13(9), e1006549.1553-7366https://hdl.handle.net/2292/71654Staphylococcus 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.Electronic-eCollectionItems in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htmCells, CulturedAnimalsHumansMiceStaphylococcus aureusStaphylococcal InfectionsEnterotoxinsExotoxinsVirulence FactorsSuperantigensImmune Evasion3107 Microbiology3207 Medical Microbiology32 Biomedical and Clinical Sciences31 Biological SciencesBiodefenseEmerging Infectious DiseasesInfectious Diseases2.1 Biological and endogenous factors2.2 Factors relating to the physical environmentInfectionScience & TechnologyLife Sciences & BiomedicineMicrobiologyParasitologyVirologyTOXIC-SHOCK-SYNDROMECLASS-IICRYSTAL-STRUCTUREBACTERIAL SUPERANTIGENS3-DIMENSIONAL STRUCTUREAUREUS BACTEREMIASTRUCTURAL BASISNASAL CARRIAGECOMPLEMENT C51107 ImmunologyBiomedicalBasic Science2.2 Factors relating to physical environment0605 Microbiology1108 Medical Microbiology3204 ImmunologyJournal Article10.1371/journal.ppat.1006549Copyright: The authors28880913 (pubmed)1553-7374PPATHOGENS-D-17-00754Attribution 4.0 Internationalhttps://creativecommons.org/licenses/by/4.0/