RESUMO
Staphylococcus aureus is a frequent commensal but also a dangerous pathogen, causing many forms of infection ranging from mild to life-threatening conditions. Among its virulence factors are lipoproteins, which are anchored in the bacterial cell membrane. Lipoproteins perform various functions in colonization, immune evasion, and immunomodulation. These proteins are potent activators of innate immune receptors termed Toll-like receptors 2 and 6. This study addressed the specific B-cell and T-cell responses directed to lipoproteins in human S. aureus carriers and non-carriers. 2D immune proteomics and ELISA approaches revealed that titers of antibodies (IgG) binding to S. aureus lipoproteins were very low. Proliferation assays and cytokine profiling data showed only subtle responses of T cells; some lipoproteins did not elicit proliferation. Hence, the robust activation of the innate immune system by S. aureus lipoproteins does not translate into a strong adaptive immune response. Reasons for this may include inaccessibility of lipoproteins for B cells as well as ineffective processing and presentation of the antigens to T cells.
Assuntos
Imunidade Adaptativa , Linfócitos B/imunologia , Proteínas de Bactérias/imunologia , Lipoproteínas/imunologia , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Linfócitos T/imunologia , Adulto , Linfócitos B/microbiologia , Células Cultivadas , Citocinas/imunologia , Feminino , Regulação da Expressão Gênica , Voluntários Saudáveis , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Proteoma/imunologia , Proteômica , Infecções Estafilocócicas/microbiologia , Linfócitos T/microbiologia , Fatores de Virulência/imunologia , Adulto JovemRESUMO
With about 25 000 molecules per cell, Asp23 is one of the most abundant proteins in Staphylococcus aureus. Asp23 has been characterized as a protein that, following an alkaline shock, accumulates in the soluble protein fraction. Transcription of the asp23 gene is exclusively regulated by the alternative sigma factor σ(B) , which controls the response of the bacterium to environmental stress. Sequence analysis identified Asp23 as a member of the widely distributed Pfam DUF322 family, precluding functional predictions based on its sequence. Using fluorescence microscopy we found that Asp23 colocalized with the cell membrane of Staphylococcus aureus. Since Asp23 has no recognizable transmembrane spanning domains, we initiated a search for proteins that link Asp23 to the cell membrane. We identified SAOUHSC_02443 as the Asp23 membrane anchor and have renamed it AmaP (Asp23 membrane anchoring protein). Deletion of the asp23 gene led to an upregulation of the cell wall stress response. In summary, we have identified Asp23 as a membrane-associated protein and we suggest a function for Asp23 in cell envelope homoeostasis.