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A mouse model for postoperative fatal enteritis due to Staphylococcus infection
Y Nakamura1, Y Aramaki, T Kakiuchi
1Third Department of Surgery, Toho University School of Medicine, 2-17-6 Ohashi, Meguro-ku, Tokyo 153-8515, Japan.
Background:
Postoperative infection of intestine with methicillin-resistant Staphylococcus aureus (MRSA) is fatal in some cases. The object of this study was to establish a mouse model for the infection, providing a useful tool for investigating mechanisms in the progression of infection.
Methods:
Mice were pretreated with cyclophosphamide, injected orally or directly into jejunum with MRSA prepared from a postoperative patient, and then given 5 daily doses of antibiotics. Forty-eight hours after the injection, bacterial translocation and serum endotoxin levels were examined. Macrophage depletion was carried out by the administration of liposome-encapsulated dichloromethylene diphosphate (Cl(2)MDP), 4 days before MRSA injection.
Results:
Injection into the jejunum but not oral administration of MRSA induced enteritis with diarrhea and resulted in death in most cyclophosphamide-treated mice. Translocation of MRSA in mesenteric lymph nodes and liver was observed, concomitantly with E. coli infection. Endotoxin-resistant C3H/HeJ mice infected with MRSA survived longer than endotoxin-sensitive C3H/He mice, but also died within a week after MRSA injection. Selective depletion of macrophages induced infection in mice that were not pretreated with cyclophosphamide.
Conclusion:
We established a mouse model for the fatal MRSA infection which induced enteritis with diarrhea, that will be a useful tool for investigating the mechanisms for sometimes fatal MRSA infection of the intestine in postoperative patients. The presence of E. coli or endotoxin seemed to play a major role in the mortality of mice in the early days of MRSA-induced enteritis, but other factors, probably from MRSA, in the later days. Phagocytes were quite important for protection against the MRSA infection.
Insights
Researchers developed a mouse model for fatal methicillin-resistant Staphylococcus aureus (MRSA) intestinal infections. This model helps study MRSA infection progression and mortality factors in postoperative patients.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Postoperative intestinal infections with methicillin-resistant Staphylococcus aureus (MRSA) can be fatal.
- Establishing a reliable animal model is crucial for understanding MRSA infection mechanisms.
Purpose of the Study:
- To create a mouse model for studying fatal MRSA intestinal infections.
- To investigate factors contributing to MRSA-induced enteritis and mortality.
Main Methods:
- Mice were immunosuppressed with cyclophosphamide and infected with MRSA via jejunal injection.
- Bacterial translocation, endotoxin levels, and macrophage activity were assessed.
- Macrophage depletion was induced using liposome-encapsulated dichloromethylene diphosphate.
Main Results:
- Jejunal MRSA injection induced fatal enteritis and diarrhea in immunosuppressed mice.
- MRSA translocation occurred in lymph nodes and liver, often with concurrent E. coli infection.
- Macrophage depletion exacerbated MRSA infection, even in non-immunosuppressed mice.
Conclusions:
- A viable mouse model for fatal MRSA intestinal infection was established.
- Early mortality appears linked to E. coli or endotoxin, while later mortality involves MRSA-specific factors.
- Phagocytic cells play a critical role in protection against MRSA infection.