Temporal and spatial dynamics of Listeria monocytogenes central nervous system infection in mice
is a bacterial pathogen that can cause life-threatening central nervous system (CNS) infections. While mechanisms by which 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 lac...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 121; no. 17; p. e2320311121 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
23.04.2024
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Subjects | |
Online Access | Get full text |
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Summary: | is a bacterial pathogen that can cause life-threatening central nervous system (CNS) infections. While mechanisms by which
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
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
population dynamics that lead to CNS infection and a framework for studying the dynamics of other cerebral infections. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.2320311121 |