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Updated: May 7, 2026
Measuring Bacterial Load and Immune Responses in Mice Infected with Listeria monocytogenes
Published on: August 9, 2011
Temporal and spatial dynamics of Listeria monocytogenes central nervous system infection in mice
Victoria Chevée1, Karthik Hullahalli2,3,4, Katherine G Dailey2,3,4
1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
Abstract:
Listeria monocytogenes is a bacterial pathogen that can cause life-threatening central nervous system (CNS) infections. While mechanisms by which L. monocytogenes and other pathogens traffic to the brain have been studied, a quantitative understanding of the underlying dynamics of colonization and replication within the brain is still lacking. In this study, we used barcoded L. monocytogenes to quantify the bottlenecks and dissemination patterns that lead to cerebral infection. Following intravenous (IV) inoculation, multiple independent invasion events seeded all parts of the CNS from the blood, however, only one clone usually became dominant in the brain. Sequential IV inoculations and intracranial inoculations suggested that clones that had a temporal advantage (i.e., seeded the CNS first), rather than a spatial advantage (i.e., invaded a particular brain region), were the main drivers of clonal dominance. In a foodborne model of cerebral infection with immunocompromised mice, rare invasion events instead led to a highly infected yet monoclonal CNS. This restrictive bottleneck likely arose from pathogen transit into the blood, rather than directly from the blood to the brain. Collectively, our findings provide a detailed quantitative understanding of the L. monocytogenes population dynamics that lead to CNS infection and a framework for studying the dynamics of other cerebral infections.
Insights
Listeria monocytogenes
Area of Science:
- Microbiology and Infectious Diseases
- Neuroscience
- Quantitative Biology
Background:
- Listeria monocytogenes is a significant bacterial pathogen causing severe central nervous system (CNS) infections.
- Understanding the quantitative dynamics of pathogen colonization and replication in the brain is crucial but lacking.
- Mechanisms of pathogen brain entry are known, but colonization dynamics remain unclear.
Purpose of the Study:
- To quantitatively analyze the population dynamics, bottlenecks, and dissemination patterns of Listeria monocytogenes during CNS infection.
- To identify factors driving clonal dominance within the brain following infection.
- To establish a framework for studying cerebral infection dynamics of various pathogens.
Main Methods:
- Utilized barcoded Listeria monocytogenes strains to track individual clones.
- Employed intravenous (IV) and intracranial inoculation models in mice.
- Investigated infection dynamics in both immunocompetent and immunocompromised models, including a foodborne model.
Main Results:
- Multiple independent invasion events seeded the CNS from the bloodstream after IV inoculation, but typically only one clone dominated the brain.
- Temporal advantage (earlier CNS seeding) was a stronger driver of clonal dominance than spatial advantage (specific brain region invasion).
- A foodborne model in immunocompromised mice showed rare invasion events leading to monoclonal CNS infection, suggesting a bottleneck during pathogen entry into the bloodstream.
Conclusions:
- Clonal dominance in Listeria monocytogenes CNS infections is primarily determined by the timing of initial colonization.
- The restrictive bottleneck for CNS infection may occur during pathogen entry into the bloodstream rather than direct brain invasion.
- This study provides quantitative insights into Listeria monocytogenes brain infection dynamics and a model for other cerebral infections.
