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Intravenous mouse infection model for studying the pathology of Enterococcus faecalis infections
Claudia Gentry-Weeks1, Monica Estay, Cindy Loui
1Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado 80523, USA. claudia.gentry-weeks@colostate.edu
Abstract:
An intravenous mouse infection model was used to compare the virulence of Enterococcus faecalis strains, to study bacterial localization and organ histopathology, and to examine the effects of Nramp1 and gamma interferon (IFN-gamma) on the course of infection. Infection of BALB/c mice with 5 x 10(8) CFU of E. faecalis JH2-2, MGH-2, 418, DS16C2, or OG1X revealed the following virulence ranking (from highest to lowest): MGH-2, 418, DS16C2, JH2-2, and OG1X. Discernible differences in the number of MGH-2 and JH2-2 bacteria were observed at 7 days (168 h) in the blood (P = 0.037), at 72 h in the liver (P = 0.002), and at 8 h in the spleen (P = 0.036). At these time points, the number of MGH-2 bacteria was higher in the blood and liver while the number of JH2-2 bacteria was higher in the spleen. At 72 h, livers from MGH-2-infected mice had higher numbers of coalescing aggregates of leukocytes and a greater degree of caseous necrosis than those from JH2-2-infected mice. These results indicate a correlation between the virulence of the E. faecalis strain, the number of bacteria in the liver, and the degree of histopathology of the liver at 72 h postinfection. IFN-gamma was important in E. faecalis infection, since IFN-gamma gene knockout mice had reduced mortality and massive coagulative necrosis was observed in wild-type mice. The contribution of Nramp1 was unclear, since Nramp1(-/-) mice and the respective control mice were innately resistant to E. faecalis. The mortality of mice in this model is probably due to induction of cytokine release and massive coagulative necrosis.
Insights
This study ranks Enterococcus faecalis strain virulence in mice, finding MGH-2 most virulent. Gamma interferon (IFN-gamma) is crucial for E. faecalis infection outcomes.
Area of Science:
- Microbiology
- Immunology
- Pathology
Background:
- Enterococcus faecalis is an opportunistic pathogen.
- Understanding strain virulence and host response is critical for infection control.
Purpose of the Study:
- To compare the virulence of different Enterococcus faecalis strains in a mouse model.
- To investigate bacterial localization, organ histopathology, and the role of Nramp1 and gamma interferon (IFN-gamma) in E. faecalis infection.
Main Methods:
- Intravenous inoculation of BALB/c mice with five different E. faecalis strains.
- Quantification of bacterial load in blood, liver, and spleen at various time points.
- Histopathological examination of infected organs.
- Comparison between wild-type and knockout mice for Nramp1 and IFN-gamma.
Main Results:
- A virulence ranking of E. faecalis strains was established: MGH-2 > 418 > DS16C2 > JH2-2 > OG1X.
- Significant differences in bacterial distribution were observed between MGH-2 and JH2-2 strains in blood, liver, and spleen.
- MGH-2 infection led to more severe liver histopathology, including leukocyte aggregates and caseous necrosis, compared to JH2-2.
- IFN-gamma knockout mice showed reduced mortality, while wild-type mice exhibited massive coagulative necrosis.
- Nramp1's contribution to E. faecalis resistance was unclear as both Nramp1(-/-) and control mice were resistant.
Conclusions:
- E. faecalis strain virulence correlates with bacterial load in the liver and the severity of liver histopathology.
- Gamma interferon (IFN-gamma) plays a significant role in host defense against E. faecalis infection.
- Mortality in this model is likely mediated by cytokine release and coagulative necrosis.