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United States Department of Agriculture

Agricultural Research Service

Title: A Prfa Transposon Mutant of Listeria Monocytogenes F2365, a Serotype 4b Strain, Is Able to Survive in the Gastrointestinal Tract But Not Cause Systemic Infection of the Spleen and Liver of Intragastrically Inoculated Mice

item Uhlich, Gaylen
item Luchansky, John
item Czuprynski, Chuck - UNIVERSITY OF WISCONSIN

Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 10, 2005
Publication Date: November 1, 2005
Citation: Faith, N., Uhlich, G.A., Luchansky, J.B., Neudeck, B., Czuprynski, C. 2005. A prfa transposon mutant of listeria monocytogenes f2365, a serotype 4b strain, is able to survive in the gastrointestinal tract but not cause systemic infection of the spleen and liver of intragastrically inoculated mice. Infection and Immunity. 73:7517-7524.

Interpretive Summary: The prfA gene of Listeria monocytogenes is a key regulatory gene that controls other genes responsible for systemic listeriosis. In rodents, which can be used as a model for human disease, the role of prfA has been studied in strains that have been injected into mice but not in strains that have been given orally. In this study we showed that a mutant strain of L. monocytogenes, which has the prfA gene inactivated, was able to survive in the mouse GI tract. However, unlike the parental strain containing prfA, which spread systemically in mice, the prfA-deficient strain was unable to spread to the liver or spleen. The prfA deficient-strain also showed less ability to survive in synthetic stomach fluid, and less ability to invade and multiply in cultured, human intestinal cells compared to the parental strain with prfA. The prfA-deficient strain was able to produce a vaccine-like protection against a subsequent virulent L. monocytogenes challenge, but the protection was not as great as that produced by a strain with prfA. This study shows that in mice, prfA is more important for systemic infection than for survival in the GI tract.

Technical Abstract: PrfA is a member of the Crp/Fnr family of global regulatory genes in Listeria monocytogenes that has been shown previously to regulate several key virulence determinants both in vitro and in parenterally inoculated laboratory rodents. However, the role of prfA in the ability of L. monocytogenes to cause infection via the gastrointestinal tract has not been clearly established. In this study, we used a prfA transposon mutant of L. monocytogenes F2365, a serotype 4b strain, to assess the role of prfA in the pathogenesis of gastrointestinal listeriosis in mice. We found that the prfA mutant was able to survive in the g.i. tract (i.e. cecum) of mice, albeit in numbers somewhat less than the wild type parent strain of L. monocytogenes. However, mice inoculated with the prfA mutant did not exhibit systemic infection of the spleen and liver, as was noted for mice inoculated with the wild type parent strain. Survival of the prfA mutant in synthetic gastric fluid at pH 2.5 or 5 was somewhat reduced as compared to the wild type strain, as was its ability to invade and multiply within differentiated human intestinal epithelial cells (Caco-2 cells). Prior infection with the prfA mutant gave mice some protection against a subsequent challenge with virulent L. monocytogenes, although much less than that gained by prior gastrointestinal infection with the wild type parent strain. These findings indicate that the global regulatory gene prfA is dispensable for colonization of the g.i. tract in mice, but not for systemic infection.

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