D-cycloserine increases the effectiveness of vancomycin against vancomycin-highly resistant Staphylococcus aureus

Vancomycin is a widely used clinical drug to treat for infection by methicillin-resistant S taphylococcus aureus . Some patients show a weak response to vancomycin treatment. We previously reported that β-lactams increase the susceptibility to vancomycin by vancomycin-highly resistant S. aureus (VRSA) strains obtained following repeated in vitro mutagenesis and vancomycin selection. Here we found that the susceptibility of the VRSA strains to vancomycin was remarkably increased by combined treatment with D -cycloserine. On the other hand, VRSA did not show increased susceptibility to vancomycin in combination with bacitracin, fosfomycin, erythromycin, lincomycin, gentamicin, levofloxacin or nisin. Furthermore, in an in vivo infection model with silkworms, combined treatment with vancomycin and D -cycloserine exhibited therapeutic effects, whereas treatment with each compound alone did not. These findings suggest that combined treatment with vancomycin and D -cycloserine could be therapeutically effective against infectious diseases caused by VRSA.