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Staphylococcus aureus Superantigen-Like Protein SSL1: A Toxic Protease

1
Department of Microbiology and Immunology, University of Mississippi Medical Center, Jackson, MS 39216, USA
2
Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, D02 PN40, Ireland
3
Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, University of Melbourne, 3000 Melbourne, Australia
*
Author to whom correspondence should be addressed.
Pathogens 2019, 8(1), 2; https://doi.org/10.3390/pathogens8010002
Received: 7 November 2018 / Revised: 12 December 2018 / Accepted: 20 December 2018 / Published: 1 January 2019
(This article belongs to the Section Human Pathogens)
Staphylococcus aureus is a major cause of corneal infections that can cause reduced vision, even blindness. Secreted toxins cause tissue damage and inflammation resulting in scars that lead to vision loss. Identifying tissue damaging proteins is a prerequisite to limiting these harmful reactions. The present study characterized a previously unrecognized S. aureus toxin. This secreted toxin was purified from strain Newman ΔhlaΔhlg, the N-terminal sequence determined, the gene cloned, and the purified recombinant protein was tested in the rabbit cornea. The virulence of a toxin deletion mutant was compared to its parent and the mutant after gene restoration (rescue strain). The toxin (23 kDa) had an N-terminal sequence matching the Newman superantigen-like protein SSL1. An SSL1 homodimer (46 kDa) had proteolytic activity as demonstrated by zymography and cleavage of a synthetic substrate, collagens, and cytokines (IL-17A, IFN-γ, and IL-8); the protease was susceptible to serine protease inhibitors. As compared to the parent and rescue strains, the ssl1 mutant had significantly reduced virulence, but not reduced bacterial growth, in vivo. The ocular isolates tested had the ssl1 gene, with allele type 2 being the predominant type. SSL1 is a protease with corneal virulence and activity on host defense and structural proteins. View Full-Text
Keywords: Staphylococcus aureus; protease; superantigen-like protein; dimerization; cytokine Staphylococcus aureus; protease; superantigen-like protein; dimerization; cytokine
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Tang, A.; Caballero, A.R.; Bierdeman, M.A.; Marquart, M.E.; Foster, T.J.; Monk, I.R.; O’Callaghan, R.J. Staphylococcus aureus Superantigen-Like Protein SSL1: A Toxic Protease. Pathogens 2019, 8, 2.

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