JAC Advance Access originally published online on February 4, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 480-486
© 2004 The British Society for Antimicrobial Chemotherapy
Effect of srtA and srtB gene expression on the virulence of Staphylococcus aureus in animal models of infection
1 Wyeth Research, 401 N. Middletown Rd., Pearl River, NY 10965; 2 Committee on Microbiology, University of Chicago, Chicago, IL, USA
Received 20 August 2003; returned 29 October 2003; revised 11 November 2003; accepted 17 November 2003
Objective: The role that the surface proteins anchored by the srtA and srtB gene products play in the ability of Staphylococcus aureus bacteria 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 LD50 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.
Keywords: sortase, virulence, arthritis, endocarditis
* Corresponding author. Tel: +1-845-602-2719; Fax: +1-845-602-5671; E-mail: weissw{at}wyeth.com
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