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Updated: May 22, 2026
High-throughput Assay to Phenotype Salmonella enterica Typhimurium Association, Invasion, and Replication in Macrophages
Published on: August 11, 2014
Dynamics of Salmonella infection of macrophages at the single cell level
Julia R Gog1, Alicia Murcia, Natan Osterman
1Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, UK.
Abstract:
Salmonella enterica causes a range of diseases. Salmonellae are intracellular parasites of macrophages, and the control of bacteria within these cells is critical to surviving an infection. The dynamics of the bacteria invading, surviving, proliferating in and killing macrophages are central to disease pathogenesis. Fundamentally important parameters, however, such as the cellular infection rate, have not previously been calculated. We used two independent approaches to calculate the macrophage infection rate: mathematical modelling of Salmonella infection experiments, and analysis of real-time video microscopy of infection events. Cells repeatedly encounter salmonellae, with the bacteria often remain associated with the macrophage for more than ten seconds. Once Salmonella encounters a macrophage, the probability of that bacterium infecting the cell is remarkably low: less than 5%. The macrophage population is heterogeneous in terms of its susceptibility to the first infection event. Once infected, a macrophage can undergo further infection events, but these reinfection events occur at a lower rate than that of the primary infection.
Insights
The probability of Salmonella infecting a macrophage is less than 5%, with initial infection rates varying. Macrophages can be reinfected, but at a lower rate than primary infection.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Salmonella enterica is an intracellular pathogen that infects macrophages, critical host cells for controlling bacterial infections.
- Understanding the dynamics of Salmonella-macrophage interactions is crucial for elucidating disease pathogenesis.
- Key parameters like the cellular infection rate have remained unquantified.
Purpose of the Study:
- To calculate the macrophage infection rate by Salmonella enterica.
- To investigate the heterogeneity in macrophage susceptibility to infection.
- To determine the rate of reinfection in macrophages.
Main Methods:
- Utilized mathematical modeling of Salmonella infection experiments.
- Employed real-time video microscopy to analyze infection events.
- Quantified bacterial association times and infection probabilities.
Main Results:
- The probability of a single Salmonella bacterium infecting a macrophage is less than 5%.
- Macrophage populations exhibit heterogeneity in susceptibility to initial Salmonella infection.
- Reinfection of already infected macrophages occurs at a lower rate than primary infection.
Conclusions:
- The low primary infection rate highlights a significant host defense mechanism.
- Macrophage heterogeneity influences Salmonella infection dynamics.
- Understanding these infection rates is fundamental for developing strategies against Salmonella infections.
