Inflammatory responses and histopathological changes in a mouse model of Staphylococcus aureus-induced bloodstream infections

Abstract

Introduction: Staphylococcus aureus-induced bloodstream infections (BSIs) remain a prevalent clinical challenge and the underlying pathogenesis is still poorly understood. The aim of this study was to investigate the inflammatory responses and histopathological changes in BSIs in mice. Methodology: Male C57BL/6 mice were inoculated with S. aureus intravenously to induce BSIs. The survival rate, weight loss, and murine sepsis scores (MSS) were monitored in BSI and phosphate-buffered saline (PBS) control mice. Blood samples and tissue homogenates were plated on agar plates to determine the bacterial burden. Inflammatory proteins and cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. Histopathologic changes were assessed by pathological inflammation score (PIS) and macroscopic and microscopic examinations. Results: BSI mice induced by 4.5 × 10 8 CFU/mL S. aureus showed ~70% survival rate, higher sepsis scores, significantly decreased body weight, elevated levels of white blood cell (WBC) counts, C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Prominent correlations were found between elevated CRP and PCT levels as well as among IL-1β, IL-6, and TNF-α. Pathological changes and higher PIS were also observed in BSI mice. Conclusions: Our results demonstrate that inflammatory proteins (PCT and CRP) and cytokines (IL-6, IL-1β and TNF-α) play an important role in the inflammatory responses and histopathological changes in S. aureus-induced BSIs.

Diabetes sepsis on Wistar rat strain (Rattus norvegicus) induced by streptozotocin and bacteria Staphylococcus aureus

“…Weight loss was significantly higher in the D and E treatment groups than in Groups B and F (unpublished data). This is in accordance with the research [8], which showed that rats induced by S. aureus bacteria concentrations of 4.5×10 4 -4.5×10 9 CFU/mL showed no weight loss. According to the research conducted by Reis et al .…”

“…The results of this study are different from those conducted by Wu et al . [8] which showed rat died after being induced with S. aureus with successive concentrations ranging from 4.5×10 7 to 4.5×10 9 CFU/mL intravenously which were observed 7 days post-infection. Death in diabetic rats is due to the impaired immune system through decreased production and function of inflammatory cytokines, loss of phagocytic function, and body antioxidant production [17].…”

“…Bacterial seeding was carried out by taking 10 colonies of S. aureus bacteria then cultured in Nutrient Broth media (Merck Millipore, Boston, USA) at 37°C for 24 h, then measuring optical density (OD) using a spectrophotometer. The results obtained with similar bacteria concentration of 0.1 OD 10 8 CFU/mL and then made appropriate dilution for treatment [8].…”

“…Wistar strain male rats were inoculated with 10 8 CFU/mL of S. aureus through asepsis IP, and the bacterial dose was 2 mL per tail. Clinical signs, weight, and survival rates were monitored daily for 3 days after infection [8].…”

“…The blood sample was then frozen for 1 h at room temperature and centrifuged at 4000xg, 4 °C, 15 min to obtain serum. The serum was further analyzed for CRP test using a commercial kit (Life Diagnostics, West Chester, AS) [8].…”