Proinflammatory exoprotein characterization of toxic shock syndrome Staphylococcus aureus

Ying-Chi Lin; Michele J Anderson; Petra L Kohler; Kristi L Strandberg; Michael E Olson; Alexander R Horswill; Patrick M Schlievert; Marnie L Peterson

doi:10.1021/bi200435n

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Proinflammatory exoprotein characterization of toxic shock syndrome Staphylococcus aureus

Journal article

Peer reviewed

Proinflammatory exoprotein characterization of toxic shock syndrome Staphylococcus aureus

Ying-Chi Lin, Michele J Anderson, Petra L Kohler, Kristi L Strandberg, Michael E Olson, Alexander R Horswill, Patrick M Schlievert and Marnie L Peterson

Biochemistry (Easton), Vol.50(33), pp.7157-7167

08/23/2011

DOI: 10.1021/bi200435n

PMCID: PMC3156861

PMID: 21749039

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Abstract

Pulsed-field gel electrophoresis (PFGE) clonal type USA200 is the most widely disseminated Staphylococcus aureus colonizer of the nose and is a major cause of toxic shock syndrome (TSS). Exoproteins derived from these organisms have been suggested to contribute to their colonization and causation of human diseases but have not been well-characterized. Two representative S. aureus USA200 isolates, MNPE (α-toxin positive) and CDC587 (α-toxin mutant), isolated from pulmonary post-influenza TSS and menstrual vaginal TSS, respectively, were evaluated. Biochemical, immunobiological, and cell-based assays, including mass spectrometry, were used to identify key exoproteins derived from the strains that are responsible for proinflammatory and cytotoxic activity on human vaginal epithelial cells. Exoproteins associated with virulence were produced by both strains, and cytolysins (α-toxin and γ-toxin), superantigens, and proteases were identified as the major exoproteins, which caused epithelial cell inflammation and cytotoxicity. Exoprotein fractions from MNPE were more proinflammatory and cytotoxic than those from CDC587 due to high concentrations of α-toxin. CDC587 produced a small amount of α-toxin, despite the presence of a stop codon (TAG) at codon 113. Additional exotoxin identification studies of USA200 strain [S. aureus MN8 (α-toxin mutant)] confirmed that MN8 also produced low levels of α-toxin despite the same stop codon. The differences observed in virulence factor profiles of two USA200 strains provide insight into environmental factors that select for specific virulence factors. Cytolysins, superantigens, and proteases were identified as potential targets, where toxin neutralization may prevent or diminish epithelial damage associated with S. aureus.

Lung - microbiology

Epithelial Cells - metabolism

Humans

Vagina - immunology

Immunoblotting

Chromatography, High Pressure Liquid

Shock, Septic - immunology

Exotoxins - metabolism

Shock, Septic - metabolism

Superantigens - metabolism

Enterotoxins - immunology

Immunoglobulin G - immunology

Swine

Cytotoxins - metabolism

Female

Lung - metabolism

Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Staphylococcal Infections - microbiology

Interleukin-8 - metabolism

Staphylococcal Infections - metabolism

Rabbits

Staphylococcal Infections - immunology

Staphylococcus aureus - isolation & purification

Exotoxins - immunology

Superantigens - immunology

Electrophoresis, Gel, Pulsed-Field

Virulence Factors

Animals

Epithelial Cells - immunology

Enterotoxins - metabolism

Staphylococcus aureus - immunology

Vagina - metabolism

Vagina - microbiology

Cytotoxins - immunology

Lung - immunology

Details

Title: Subtitle: Proinflammatory exoprotein characterization of toxic shock syndrome Staphylococcus aureus
Creators: Ying-Chi Lin - Department of Experimental and Clinical Pharmacology, College of Pharmacy, Medical School University of Minnesota, Minneapolis, Minnesota 55455, USA
Michele J Anderson
Petra L Kohler
Kristi L Strandberg
Michael E Olson
Alexander R Horswill
Patrick M Schlievert
Marnie L Peterson
Resource Type: Journal article
Publication Details: Biochemistry (Easton), Vol.50(33), pp.7157-7167
DOI: 10.1021/bi200435n
PMID: 21749039
PMCID: PMC3156861
NLM abbreviation: Biochemistry
ISSN: 0006-2960
eISSN: 1520-4995
Publisher: United States
Grant note: U54-AI57153 / NIAID NIH HHS AI-07511 / NIAID NIH HHS R01 AI073366 / NIAID NIH HHS R01 AI078921 / NIAID NIH HHS AI-74283 / NIAID NIH HHS R01 AI078921-04 / NIAID NIH HHS AI-73366 / NIAID NIH HHS R01 AI074283 / NIAID NIH HHS T32 AI007511 / NIAID NIH HHS U54 AI057153-08 / NIAID NIH HHS AI-078921 / NIAID NIH HHS U54 AI057153 / NIAID NIH HHS R01 AI074283-23 / NIAID NIH HHS R01 AI073366-03 / NIAID NIH HHS
Language: English
Date published: 08/23/2011
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001216002771

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