title: Nitric oxide mediated Staphylococcus aureus pathogenesis and protective role of nanoconjugated vancomycin.
abstract: 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.
authors.affiliation: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore-721102, West Bengal, India.
authors.forename: Subhankari Prasad
authors.initials: SP
authors.lastname: Chakraborty
authors.forename: Santanu Kar
authors.initials: SK
authors.lastname: Mahapatra
authors.forename: Sumanta Kumar
authors.initials: SK
authors.lastname: Sahu
authors.forename: Sourav
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Panchanan
authors.initials: P
authors.lastname: Pramanik
authors.forename: Somenath
authors.initials: S
authors.lastname: Roy
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D016470:Bacteremia / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009569:Nitric Oxide / Q000276:immunology*; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D014640:Vancomycin / Q000008:administration & dosage* / Q000737:chemistry; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D009569:Nitric Oxide; D014640:Vancomycin
keywords: Anti-inflammatory; Antioxidant enzymes; Antioxidative effect; Bacteremia; IL-10; Infection; Inflammatory parameter; Lymphocyte; Nanoconjugated vancomycin; Nitric oxide; Oxidative stress; Pathogenesis; Staphylococcus aureus; TNF-α