Fosfomycin Reduces CD15s-Related Antigen Expression ofStreptococcus pyogenes

We have previously shown the immunological mimicry of human sialyl-Lewisx (CD15s) by a surface antigen ofStreptococcus pyogenes . This mimicking surface antigen may act as a ligand to the selectin family and may induce antibody production against CD15s on host cells, suggesting a possible role in the pathogenesis ofS. pyogenes . In this study, the effects of antibiotics on the CD15s-related antigen expression ofS. pyogenes were examined at a concentration below the MIC (sub-MIC). The amounts of CD15s on the surfaces ofS. pyogenes cells and on the surfaces ofS. pyogenes biofilms were determined by a whole-cell enzyme-linked immunosorbent assay and by laser scanning fluorescence microscopy, respectively, by using an anti-CD15s monoclonal antibody. At the sub-MICs, fosfomycin (1R ,2S -1,2-epoxypropyl phosphonic acid), its enantiomer (1S ,2R -1,2-epoxypropyl phosphonic acid), and benzylpenicillin significantly inhibited the CD15s expression of all strains studied. The effects of fosfomycin and its enantiomer on biofilms were also observed by scanning electron microscopy. Incubation ofS. pyogenes with the sub-MIC of fosfomycin or its enantiomer, which has no antibacterial activity, reduced the amount of CD15s on the biofilm surface and made it smooth. These results suggest that fosfomycin or its enantiomer might be useful for preventingS. pyogenes adherence to human CD15s receptors and the resulting immunological pathogenicity.