Establishment and evaluation of mouse models of Staphylococcus aureus and Klebsiella pneumoniae bloodstream infections

Abstract

Objective To establish the reliable models for early diagnosis of bloodstream infections by common clinical bacteria and to provide reliable experimental models for screening and validation of biomarkers in the early stage of bacterial bloodstream infections. Methods Strains of Staphylococcus aureus (S.aureus) ATCC25923 and Klebsiella pneumoniae (K.pneumoniae) ATCC700603 were used as experimental strains. Different concentrations of bacterial suspensions were injected into mice through tail vein. LD50 (median lethal dose) was calculated by Karber method and the concentration of 1/2LD50 was used for injection. The established mouse models were evaluated based on the changes in physical signs, body weights, white blood cells (WBC), platelets and IL-6 as well as the results of blood culture, PCR and HE staining. Results LD50 of S. aureus and K. pneumoniae to ICR mice were 8.1×108 CFU/ml and 1.11×109 CFU/ml, respectively. Body weights of mice decreased significantly at the time point of 24 h after infection. WBC counts in normal mice were about (1.42±0.66)×109/L, but increased in model groups at 3 h after bacteria challenge. Compared with the control group, WBC counts in model groups increased significantly at 6 h (P<0.05), followed by decreases. Two days after infection, WBC counts in model groups increased again and remained at high levels till the 7th day. However, PLT counts in the model groups dropped dramatically within 2 days as compared with that in control group (P<0.05). Increase of IL-6 was detected in the early K. pneumoniae infection and the extent of that was larger than that in S. aureus infection. Results of the whole blood culture were all positive within 2 days after infection. PCR analysis confirmed that the bloodstream infection pathogens were S. aureus and K. pneumoniae. Alveolar exudation, edema and leukocyte infiltration were observed in lung and liver tissues with HE staining. Conclusion The mouse models of S. aureus and K. pneumoniae infections for early detection of bloodstream infections are successfully established. This study provides reliable animal models for further researches on early diagnosis of different pathogen-induced bloodstream infections. Key words: Staphylococcus aureus; Klebsiella pneumonia; Virulence factor; Bloodstream infection model