Journal article
The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function
PLoS pathogens, Vol.13(9), pp.e1006461-e1006461
09/2017
DOI: 10.1371/journal.ppat.1006461
PMCID: PMC5589267
PMID: 28880920
Abstract
Bacterial superantigens (SAgs) cause Vβ-dependent T-cell proliferation leading to immune dysregulation associated with the pathogenesis of life-threatening infections such as toxic shock syndrome, and necrotizing pneumonia. Previously, we demonstrated that staphylococcal enterotoxin-like toxin X (SElX) from Staphylococcus aureus is a classical superantigen that exhibits T-cell activation in a Vβ-specific manner, and contributes to the pathogenesis of necrotizing pneumonia. Here, we discovered that SElX can also bind to neutrophils from human and other mammalian species and disrupt IgG-mediated phagocytosis. Site-directed mutagenesis of the conserved sialic acid-binding motif of SElX abolished neutrophil binding and phagocytic killing, and revealed multiple glycosylated neutrophil receptors for SElX binding. Furthermore, the neutrophil binding-deficient mutant of SElX retained its capacity for T-cell activation demonstrating that SElX exhibits mechanistically independent activities on distinct cell populations associated with acquired and innate immunity, respectively. Finally, we demonstrated that the neutrophil-binding activity rather than superantigenicity is responsible for the SElX-dependent virulence observed in a necrotizing pneumonia rabbit model of infection. Taken together, we report the first example of a SAg, that can manipulate both the innate and adaptive arms of the human immune system during S. aureus pathogenesis.
Details
- Title: Subtitle
- The Staphylococcus aureus superantigen SElX is a bifunctional toxin that inhibits neutrophil function
- Creators
- Stephen W Tuffs - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland, United States of AmericaDavid B A James - Department of Microbiology, New York University School of Medicine, New York, NY, United KingdomJovanka Bestebroer - Department Medical Microbiology, UMC Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The NetherlandsAmy C Richards - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland, United States of AmericaMariya I Goncheva - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland, United States of AmericaMarie O'Shea - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland, United States of AmericaBryan A Wee - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland, United States of AmericaKeun Seok Seo - Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, MS, United StatesPatrick M Schlievert - Department of Microbiology, University of Iowa, Carver College of Medicine, Iowa City, Iowa, United States of AmericaAndreas Lengeling - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland, United States of AmericaJos A van Strijp - Department Medical Microbiology, UMC Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The NetherlandsVictor J Torres - Department of Microbiology, New York University School of Medicine, New York, NY, United KingdomJ Ross Fitzgerald - The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian, Scotland, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.13(9), pp.e1006461-e1006461
- DOI
- 10.1371/journal.ppat.1006461
- PMID
- 28880920
- PMCID
- PMC5589267
- NLM abbreviation
- PLoS Pathog
- ISSN
- 1553-7366
- eISSN
- 1553-7374
- Publisher
- United States
- Grant note
- BB/I013873/1 / Biotechnology and Biological Sciences Research Council P20 GM103646 / NIGMS NIH HHS
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001205802771
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