Effect of srtA and srtB gene expression on the virulence of Staphylococcus aureus in animal models of infection

Objective: The role that the surface proteins anchored by the srtA and srtB gene products play in the ability of Staphylococcusaureusbacteria to establish infection was investigated in several animal models. Methods: Wild-type and corresponding mutants with deletions of the srtA and/or srtB genes were used in murine acute lethal infection, septic arthritis, kidney infection and rat endocarditis models. Results: The LD 50 of the wild-type and srtB- knockout were comparable and approximately two- to four-fold lower than the required inoculum of the srtA-and srtA-B- strains. This difference was exhibited as a two-fold greater mortality at the highest inoculum. The wild-type strain established arthritic inflammation in over 90% of the animals with a maximum arthritic index of 6.5 by days 17-21. The srtB- knockout was able to cause inflammation in 70-80% of the mice, but with a lower index of 3.0. Both the srtA- and srtA-B- strains appeared to be less virulent in this model with arthritic indices of around 0.5 and only 20% of the animals with inflammation. Strains with the srtA mutation achieved statistically significant lower titres than wild-type in kidneys of mice after intravenous infection. Mean bacterial counts in cardiac vegetations were significantly higher for the wild-type and srtB- strain compared with the srtA- and srtA-B- strains. Conclusion: Results from this study substantiate the role of the srtA gene product in the establishment of infections and further studies are warranted to define and exploit this as a target for antimicrobial chemotherapy.