title: 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.
authors: Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, Serdang, Malaysia School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia.
authors: Yun Khoon
authors: YK
authors: Liew
authors: Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, Serdang, Malaysia.
authors: Rukman
authors: R
authors: Awang Hamat
authors: bioMérieux, La Balme Microbiology Unit, La Balme les Grottes, France.
authors: Alex
authors: A
authors: van Belkum
authors: Department of Biomedical Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
authors: Pei Pei
authors: PP
authors: Chong
authors: Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, Serdang, Malaysia vasantha@upm.edu.my.
authors: Vasanthakumari
authors: V
authors: Neela
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D016470:Bacteremia / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D001426:Bacterial Proteins / Q000032:analysis* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D054370:Chemokine CXCL9 / Q000097:blood; D018925:Chemokines / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D015180:Electrophoresis, Gel, Two-Dimensional; D054884:Host-Pathogen Interactions; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D040901:Proteomics; D018461:Soft Tissue Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013203:Staphylococcal Infections / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D013207:Staphylococcal Skin Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D053719:Tandem Mass Spectrometry
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; D054370:Chemokine CXCL9; D018925:Chemokines; D016207:Cytokines