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Updated: Jun 17, 2026
Chronic Salmonella Infected Mouse Model
Published on: May 31, 2010
Thioridazine protects the mouse from a virulent infection by Salmonella enterica serovar Typhimurium 74
Asish Dasgupta1, Sayanti Mukherjee, Shaswati Chaki
1Department of Microbiology, Herbicure Healthcare Bio-Herbal Research Foundation, 7 & 8 Metro Garden City, D.H. Road, Pailan, Kolkata 700107, India.
Abstract:
When administered to mice at doses of 100microg/mouse and 200microg/mouse, thioridazine (TDZ) significantly protected animals from the lethality produced by a virulent strain of Salmonella enterica serovar Typhimurium and reduced the number of bacteria retrieved from the spleen, liver and heart blood. The protection conferred by TDZ against a virulent Salmonella infection is hypothesised to be due to a reduction in the 55kDa virulence protein of the outer membrane of the organism, as this protein is almost totally absent when the organism is exposed to the phenothiazine. It is further hypothesised that the reduction in the 55kDa virulence factor renders the organism susceptible to the action of hydrolytic enzymes of the neutrophil phagolysosome, whereas in the absence of exposure to TDZ intracellular ingestion and localisation of the phagocytosed bacterium does not result in killing owing to rapid induction of the two-step PmrA/B regulon that results in the eventual synthesis and insertion of lipid A into the nascent lipopolysaccharide layer of the outer membrane.
Insights
Thioridazine (TDZ) protects mice against Salmonella Typhimurium lethality by reducing a key virulence protein. This allows immune cells to kill the bacteria, offering a potential therapeutic strategy for Salmonella infections.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Salmonella enterica serovar Typhimurium is a virulent pathogen causing significant lethality.
- The 55kDa outer membrane protein is crucial for Salmonella virulence.
- Neutrophil phagolysosome activity is key to bacterial clearance.
Purpose of the Study:
- To investigate the protective effects of thioridazine (TDZ) against Salmonella Typhimurium infection in mice.
- To elucidate the mechanism by which TDZ confers protection.
Main Methods:
- Administration of thioridazine (TDZ) to mice at varying doses.
- Infection of mice with a virulent strain of Salmonella Typhimurium.
- Quantification of bacterial load in spleen, liver, and heart blood.
- Analysis of outer membrane protein expression in Salmonella exposed to TDZ.
Main Results:
- Thioridazine (TDZ) administration significantly reduced mortality in mice infected with Salmonella Typhimurium.
- TDZ treatment led to a marked decrease in bacterial counts in host organs.
- Exposure to TDZ resulted in the near-total absence of the 55kDa outer membrane virulence protein.
Conclusions:
- Thioridazine (TDZ) exhibits significant protective effects against virulent Salmonella Typhimurium infection in a murine model.
- The protective mechanism is likely mediated by the downregulation of a critical 55kDa virulence factor, rendering Salmonella susceptible to host immune defenses.
- TDZ may represent a novel therapeutic agent for combating Salmonella infections by interfering with bacterial virulence mechanisms.
