Mouse Study Identifies Molecular Mechanism behind Bacterial Meningitis

A team of molecular microbiologists examined the ability of the bacterium Salmonella enterica serovar Typhimurium to infect the central nervous system and cause meningitis following the natural route of infection in mice.

Investigators at the [U.S.] National Institute of Allergy and Infectious Diseases Rocky Mountain Laboratories (Hamilton, MT, USA) worked with two lines of C57BL/6J mic. These animals are extremely susceptible to systemic infection by Salmonella Typhimurium because of loss-of-function mutations in Nramp1 (Natural resistance-associated macrophage protein 1), a phagosomal membrane protein that controls iron export from vacuoles and inhibits Salmonella growth in macrophages.

In the current study, the investigators assessed the ability of Salmonella to disseminate to the central nervous system (CNS) after oral infection in C57BL/6J mice expressing either wild-type (resistant) or mutant (susceptible) alleles of Nramp1. They reported in the December 9, 2016, online edition of the American Journal of Pathology that in both strains, oral infection resulted in focal meningitis and ventriculitis with recruitment of inflammatory monocytes to the CNS. In the susceptible Nramp1−/− mice, there was a direct correlation between bacteremia and the number of bacteria in the brain, which was not observed in resistant Nramp1+/+ mice.

The investigators concluded that Nramp1 was not essential for Salmonella entry into the CNS or neuroinflammation, but may have influenced the mechanisms of CNS entry as well as the severity of meningitis.

Related Links:
[U.S.] National Institute of Allergy and Infectious Diseases