title: Levels of alpha-toxin correlate with distinct phenotypic response profiles of blood mononuclear cells and with agr background of community-associated Staphylococcus aureus isolates.
abstract: Epidemiological studies of Staphylococcus aureus have shown a relation between certain clones and the presence of specific virulence genes, but how this translates into virulence-associated functional responses is not fully elucidated. Here we addressed this issue by analyses of community-acquired S. aureus strains characterized with respect to antibiotic resistance, ST types, agr types, and virulence gene profiles. Supernatants containing exotoxins were prepared from overnight bacterial cultures, and tested in proliferation assays using human peripheral blood mononuclear cells (PBMC). The strains displayed stable phenotypic response profiles, defined by either a proliferative or cytotoxic response. Although, virtually all strains elicited superantigen-mediated proliferative responses, the strains with a cytotoxic profile induced proliferation only in cultures with the most diluted supernatants. This indicated that the superantigen-response was masked by a cytotoxic effect which was also confirmed by flow cytometry analysis. The cytotoxic supernatants contained significantly higher levels of α-toxin than did the proliferative supernatants. Addition of α-toxin to supernatants characterized as proliferative switched the response into cytotoxic profiles. In contrast, no effect of Panton Valentine Leukocidin, δ-toxin or phenol soluble modulin α-3 was noted in the proliferative assay. Furthermore, a significant association between agr type and phenotypic profile was found, where agrII and agrIII strains had predominantly a proliferative profile whereas agrI and IV strains had a predominantly cytotoxic profile. The differential response profiles associated with specific S. aureus strains with varying toxin production could possibly have an impact on disease manifestations, and as such may reflect specific pathotypes.
authors.affiliation: Karolinska Institutet, Centre for Infectious Medicine, Stockholm, Sweden.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Mairpady Shambat
authors.affiliation: Karolinska Institutet, Centre for Infectious Medicine, Stockholm, Sweden.
authors.forename: Axana
authors.initials: A
authors.lastname: Haggar
authors.affiliation: CIRI, International Center for Infectiology Research, LabEx Ecofect, Université Lyon 1, Inserm U1111, Ecole Normale Supérieure de Lyon, CNRS UMR5308, Centre National de Référence des Staphylocoques, Hospices civils de Lyon, Lyon, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Vandenesch
authors.affiliation: CIRI, International Center for Infectiology Research, LabEx Ecofect, Université Lyon 1, Inserm U1111, Ecole Normale Supérieure de Lyon, CNRS UMR5308, Centre National de Référence des Staphylocoques, Hospices civils de Lyon, Lyon, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Lina
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, Rotterdam, Netherlands.
authors.forename: Willem J B
authors.initials: WJ
authors.lastname: van Wamel
authors.affiliation: Society for Innovation and Development, Indian Institute of Science Campus, Bangalore, India.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Arakere
authors.affiliation: Karolinska Institutet, Centre for Infectious Medicine, Stockholm, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Svensson
authors.affiliation: Karolinska Institutet, Centre for Infectious Medicine, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Norrby-Teglund
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D017714:Community-Acquired Infections / Q000097:blood / Q000382:microbiology*; D024881:Drug Resistance, Bacterial; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D010641:Phenotype; D013203:Staphylococcal Infections / Q000097:blood* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000145:classification / Q000276:immunology / Q000302:isolation & purification*; D018089:Superantigens / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D018089:Superantigens