D-114. The Role of the Panton-Valentine Leukocidin (PVL) in Virulence of Staphylococcus aureus in a Mouse Skin Abscess Infection Model

P. Yoong, G. B. Pier;
Harvard Med. Sch., Boston, MA.

Background: Community-acquired infections caused by methicillin resistant S. aureus (CA-MRSA) are increasing in frequency and generating a great deal of concern. CA-MRSA strains often express the Panton-Valentine leukocidin (PVL). The contribution of PVL to bacterial virulence in a variety of tissues has not been firmly established and published reports are contradictory in this regard. We have previously shown in a mouse model of pneumonia (Yoong & Pier, Abstract D-113, ASM GM 2007) that knocking out PVL (ΔPVL) increased the virulence of S. aureus, causing higher mortality in mice than isogenic PVL-producing counterparts. We sought to examine if PVL plays an analogous role in a different model of S. aureus infection, that of foreign-body dependent skin abscesses in mice. Methods: 3-5 week old Swiss-Webster mice were anesthetized then inoculated intradermally, midback, with a 100 μL S. aureus suspension containing 105 CFU. Infections proceeded for 72 hours, followed by excision of abscesses. Infection with isogenic wild-type (WT) and ΔPVL strains of S. aureus NRS193 and NRS194 were compared. Also, normal rabbit serum or rabbit antibodies to recombinant PVL were given IP, followed by infection with PVL-producing S. aureus strains, to determine the effects on skin infection. Results: The ΔPVL S. aureus strains replicated more efficiently within skin abscesses. Higher bacterial numbers were recovered following infection with ΔPVL strains NRS193 and NRS194 compared with WT strains. Abscesses from mice given antibody to PVL then infected with PVL-producing strains USA300, NRS157, NRS193 and NRS194 also had significantly higher bacterial counts than mice given normal sera. Conclusions: Taken together, the results from 2 mouse models of S. aureus infections (pneumonia and abscess) suggest that PVL does not appear to enhance bacterial virulence, but may protect the host, possibly via activation of innate immunity. In the absence of PVL, or following neutralization of PVL with antibody, host responses may be delayed or diminished, allowing S. aureus to better replicate and overwhelm the host, thereby enhancing bacterial virulence.