Nitric oxide mediated Staphylococcus aureus pathogenesis and protective role of nanoconjugated vancomycin.

OBJECTIVE: To test the survival of Staphylococcus aureus (S. aureus) inside lymphocyte that contributes to the pathogenesis of infection and possible anti-inflammatory and antioxidative effect of nanoconjugated vancomycin against in vivo S. aureus infection in a dose and duration dependent manner. METHODS: 5×10(6) CFU/mL vancomycin-sensitive S. aureus (VSSA) and vancomycin-resistive S. aureus (VRSA) were challenged in Swiss male mice for 3 days, 5 days, 10 days and 15 days, respectively. Bacteremia and inflammatory parameters were observed to evaluate the duration for development of VSSA and VRSA infection. 100 mg/kg bw/day and 500 mg/kg bw/day nanoconjugated vancomycin were administrated to VSSA and VRSA infected group for 5 days. Bacteremia, inflammatory parameters and oxidative stress related parameters were tested to observe the effective dose of nanoconjugated vancomycin against VSSA and VRSA infection. Nanoconjugated vancomycin was treated at a dose of 100 mg/kg bw/day and 500 mg/kg bw/day, respectively, to VSSA and VRSA infected group for successive 5 days, 10 days and 15 days. Bacteremia, inflammatory parameters and oxidative stress related parameters were observed to assess the effective duration of nanoconjugated vancomycin against VSSA and VRSA infection. RESULTS: The result revealed that in vivo VSSA and VRSA infection developed after 5 days of challenge by elevating the NO generation in lymphocyte and serum inflammatory markers. Administration with nanoconjugated vancomycin to VSSA and VRSA infected group at a dose of 100 mg/kg bw/day and 500 mg/kg bw/day, respectively, for successive 10 days eliminated bacterimia, decreased NO generation in lymphocyte, serum inflammatory markers and increased antioxidant enzyme status. CONCLUSIONS: These findings suggest, in vivo challenge of VSSA and VRSA for 5 days can produce the highest degree of damage in lymphocyte which can be ameliorated by treatment with nanoconjugated vancomycin for 10 successive days.