Background
Staphylococcus aureus is the leading cause of infective endocarditis (IE), a steadily increasing disease. IE is often associated with age and heart valve transplantation, but also affects intravenous (i.v.) drug users. The mortality rate of IE is high and therapy is complicated by the variety of S. aureus strains including resistances to several antibiotics. Aims of this study were to decipher bacterial proteins required to establish IE and screening for differences that might explain the varying outcome of normal IE patients (NDU) vs. i.v. drug users (IDU). Here, we used a multi-omics approach to study whether bacterial factors (genomics, proteomics) or the host’s antibody response (immunoproteomics) impact the IE outcome.
Methods
The secretome and intracellular proteome of 25 S. aureus strains from IE patients (11 IDU, 14 NDU) and 25 strains from healthy carriers, which were matched for clonal clusters, were analyzed by nanoLC-MS/MS after cultivation in RPMI medium until stationary phase. Data analysis was done with a multi-strain database. The plasma of IE patients (28 days vs. disease onset) was analyzed by immunoproteomics using the xMAP® technology with a panel of 80 recombinant S. aureus antigens.
Results
Differences between IE causing strains and controls occurred in metabolism, cell surface proteins, proteins encoded by mobile genetic elements, and in the virulence factor repertoire. IE strains also displayed increased production of proteins involved in attachment to e.g., heart valves. Immunoproteomics revealed an increase in antibody titers against secreted toxins and immune evasion factors during the course of IE as well as differences between responses of IDU and NDU.
Conclusion
IE strains differ from colonizing strains in abundances of particular proteins. Moreover, higher anti-S. aureus antibody titers at disease onset as well as during infection might contribute to the better outcome of IDU patients.