Background. Vancomycin has been the mainstay treatment for patients with MRSA bacteraemia. However, extended hospitalization and poor treatment outcomes can be caused by Staphylococcus aureus with reduced susceptibility to vancomycin. Infection by vancomycin intermediate S. aureus (VISA) is usually non-fatal but difficult to eradicate. The purpose of this study was to compare the pathogenicity of clinical VISA strains with their vancomycin sensitive S. aureus (VSSA) parent strains.
Methods. A collection of VSSA/VISA isolate pairs was tested for exotoxin production using alpha toxin western immunoblotting. An agr reporter assay was employed to assess agr functionality. The virulence potential of VSSA and VISA were compared in a murine infection model and blood serum cytokine levels of infected mice were measured.
Results. We showed that all VISA strains were attenuated for virulence in our mammalian bacteraemia model compared to their VSSA parent strains. Despite their inability to cause life-threatening disease, VISA strains persisted in vivo for at least 14 days. These data may be at least partly explained by a significant reduction in exotoxin production in VISA strains and altered agr expression. Additionally, host responses to VSSA/VISA were different, with interleukin-6 levels being significantly lower in mice infected with VISA strains, which could favour persistence.
Conclusions. Taken together, these findings show that VISA strains were less virulent than their VSSA parent strains but were able to persist in vivo, which may be due to altered expression and production of bacterial virulence factors and/or altered host immune responses.