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The superantigenic toxin of Yersinia pseudotuberculosis: a novel virulence factor?
C Carnoy1, H Müller-Alouf, P Desreumaux
1Equipe Mixte INSERM E 9919, Université JE 2225, Institut de Biologie de Lille, France. christophe.carnoy@ibl.fr
Abstract:
Recently, a superantigenic toxin designated YPM (Yersinia pseudotuberculosis-derived mitogen) was characterized in the supernatant of Y. pseudotuberculosis, a Gram-negative bacterium involved in human enteric infection. To assess the role of YPM in pathophysiology of Y. pseudotuberculosis, a superantigen-deficient mutant was constructed and its virulence was tested in a murine model of infection and compared with the virulence of the wild-type strain (wt). Determination of the survival rate after intravenous inoculation of mice clearly demonstrated a higher survival rate when animals were infected with the superantigen-deficient strain. This decreased virulence of the mutant strain could not be explained by a lower bacterial growth rate in spleen, liver or lung of infected animals. Therefore, production of IFNgamma, TNFalpha, IL-2, IL-6 and IL-10 was followed during the course of infection by cytokine assay in the blood and mRNA detection in the spleen. IL-6 and IFNgamma were the two major cytokines detected whereas TNFalpha production was never observed.
Insights
Yersinia pseudotuberculosis-derived mitogen (YPM) contributes to infection severity. A YPM-deficient mutant showed reduced virulence in mice, indicating YPM
Area of Science:
- Microbiology
- Immunology
- Pathogen Research
Background:
- Yersinia pseudotuberculosis is a Gram-negative bacterium causing human enteric infections.
- A superantigenic toxin, Yersinia pseudotuberculosis-derived mitogen (YPM), is secreted by Y. pseudotuberculosis.
- The role of YPM in Y. pseudotuberculosis pathophysiology remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of YPM in the virulence of Y. pseudotuberculosis.
- To compare the pathogenicity of a YPM-deficient mutant with the wild-type strain in a murine model.
- To analyze the cytokine response during infection with Y. pseudotuberculosis strains with and without YPM.
Main Methods:
- Construction of a superantigen-deficient Y. pseudotuberculosis mutant.
- Intravenous inoculation of mice with wild-type and mutant strains.
- Assessment of survival rates, bacterial growth in organs (spleen, liver, lung), and cytokine profiles (IFN-gamma, TNF-alpha, IL-2, IL-6, IL-10) in blood and spleen.
Main Results:
- Mice infected with the YPM-deficient mutant exhibited a significantly higher survival rate compared to those infected with the wild-type strain.
- Bacterial growth rates in the spleen, liver, and lungs were comparable between the mutant and wild-type infections.
- Elevated levels of IL-6 and IFN-gamma were detected during infection, with IL-6 and IFN-gamma being the predominant cytokines. TNF-alpha production was not observed.
Conclusions:
- YPM plays a significant role in the pathophysiology and virulence of Y. pseudotuberculosis infections.
- The reduced virulence of the YPM-deficient mutant is not attributable to impaired bacterial proliferation.
- YPM influences the host's immune response, particularly cytokine production, contributing to disease severity.