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Comparative Exoproteomics and Host Inflammatory Response in Staphylococcus aureus Skin and Soft Tissue Infections, Bacteremia, and Subclinical Colonization.

Abstract
The exoproteome of Staphylococcus aureus contains enzymes and virulence factors that are important for host adaptation. We investigated the exoprotein profiles and cytokine/chemokine responses obtained in three different S. aureus-host interaction scenarios by using two-dimensional gel electrophoresis (2-DGE) and two-dimensional immunoblotting (2D-IB) combined with tandem mass spectrometry (MS/MS) and cytometric bead array techniques. The scenarios included S. aureus bacteremia, skin and soft tissue infections (SSTIs), and healthy carriage. By the 2-DGE approach, 12 exoproteins (the chaperone protein DnaK, a phosphoglycerate kinase [Pgk], the chaperone GroEL, a multisensor hybrid histidine kinase, a 3-methyl-2-oxobutanoate hydroxymethyltransferase [PanB], cysteine synthase A, an N-acetyltransferase, four isoforms of elongation factor Tu [EF-Tu], and one signature protein spot that could not be reliably identified by MS/MS) were found to be consistently present in more than 50% of the bacteremia isolates, while none of the SSTI or healthy-carrier isolates showed any of these proteins. By the 2D-IB approach, we also identified five antigens (methionine aminopeptidase [MetAPs], exotoxin 15 [Set15], a peptidoglycan hydrolase [LytM], an alkyl hydroperoxide reductase [AhpC], and a haptoglobin-binding heme uptake protein [HarA]) specific for SSTI cases. Cytokine and chemokine production varied during the course of different infection types and carriage. Monokine induced by gamma interferon (MIG) was more highly stimulated in bacteremia patients than in SSTI patients and healthy carriers, especially during the acute phase of infection. MIG could therefore be further explored as a potential biomarker of bacteremia. In conclusion, 12 exoproteins from bacteremia isolates, MIG production, and five antigenic proteins identified during SSTIs should be further investigated for potential use as diagnostic markers.
AuthorsYun Khoon Liew, Rukman Awang Hamat, Alex van Belkum, Pei Pei Chong, Vasanthakumari Neela
JournalClinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 22 Issue 5 Pg. 593-603 (May 2015) ISSN: 1556-679X [Electronic] United States
PMID25809633 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Biomarkers
  • Chemokine CXCL9
  • Chemokines
  • Cytokines
Topics
  • Antibodies, Bacterial (blood)
  • Bacteremia (immunology, metabolism, microbiology)
  • Bacterial Proteins (analysis, immunology)
  • Biomarkers (blood)
  • Chemokine CXCL9 (blood)
  • Chemokines (blood, immunology)
  • Cytokines (blood, immunology)
  • Electrophoresis, Gel, Two-Dimensional
  • Host-Pathogen Interactions
  • Humans
  • Inflammation
  • Male
  • Middle Aged
  • Pilot Projects
  • Proteomics
  • Soft Tissue Infections (immunology, metabolism, microbiology)
  • Staphylococcal Infections (immunology, metabolism, microbiology)
  • Staphylococcal Skin Infections (immunology, metabolism, microbiology)
  • Staphylococcus aureus (metabolism, pathogenicity)
  • Tandem Mass Spectrometry

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