Staphylococcus aureusCorneal Infections: Effect of the Panton-Valentine Leukocidin (PVL) and Antibody to PVL on Virulence and Pathology

Abstract

Community-associated methicillin-resistant Staphylococcus aureus strains expressing Panton-Valentine leukocidin (PVL) are associated with severe skin and soft tissue infections, necrotizing pneumonia, and eye infections. We determined PVL's toxicity on infected mouse and cultured human corneal epithelial cells and the role of PVL and antibody to PVL in pathogenesis of murine keratitis. Cytotoxicity on corneas and corneal epithelial cells was evaluated by LDH assays. Scratched corneas of female A/J mice were inoculated with approximately 10⁷ CFU/eye of either WT S. aureus, isogenic ΔPVL, or strains overproducing PVL. Antibodies to PVL or control sera were topically applied to infected corneas 0, 24, and 32 hours postinfection, corneas scored for pathology and tissue levels of S. aureus were determined. PVL expression augmented the cytotoxicity of S. aureus on infected mouse corneas and human cultured corneal epithelial cells. Variable effects on leukocyte recruitment, pathogenesis, and immunity were obtained in the in vivo studies. Inactivation of PVL in USA300 strains caused reduced pathology and bacterial counts. Results were variable when comparing WT and ΔPVL USA400 strains, while USA400 strains overproducing PVL caused increased bacterial burdens. Topical treatment with polyclonal antibody to PVL yielded significant reductions in corneal pathology and bacterial CFU in corneas infected with USA300 strains, whereas effects were inconsistent in eyes infected with USA400 strains. PVL enhanced the virulence of a subset of MRSA strains in a keratitis model. Coupled with a variable effect of antibody treatment, it appears that PVL plays an inconsistent role in pathogenesis and immunity to S. aureus corneal infection.