Salmonella infection in the murine brain

National Institute Of Allergy And Infectious Diseases

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Abstract

The purpose of the study is to investigate bacterial meningitis using a mouse model of infection with Salmonella Typhimurium. We are using various mouse strains that have genetically different susceptibilities to infection with Salmonella Typhimurium. C57BL/6 mice are very susceptible due to an inactivating mutation in the natural resistance-associated macrophage protein 1 (NRAMP1). Nramp1 exerts pleiotropic effects on macrophage functions and plays an important role in the control of several intracellular bacterial pathogens including Salmonella Typhimurium. Genetically susceptible Nramp1-/- C57BL/6 mice are being compared to Nramp+/+ reconstituted C57BL/6 mice that develop a controlled sustained infection over several weeks. Following oral or intravenous administration of Salmonella Typhimurium, viable can be isolated Salmonella from the brains of both Nramp1-/- and Nramp1+/+ mice within 3-6 days. A small number of Nramp1+/+ mice develop severe ataxia and have very high bacterial burdens in the brain (2-3 logs higher than in any others) and histological signs of severe meningioencephalitis, vasculitis and abscesses, all of which are characteristic of Salmonella meningitis in humans.