Temporal and spatial dynamics of Listeria monocytogenes central nervous system infection in mice

• 成果类型: Article
• 署名作者: Chevee, Victoria; Hullahalli, Karthik; Dailey, Katherine G.; Guereca, Leslie; Zhang, Chenyu; Waldor, Matthew K.; Portnoy, Daniel A.
• 署名单位: University of California System; University of California Berkeley; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Howard Hughes Medical Institute; University of California System; University of California Berkeley
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10931
• DOI: 10.1073/pnas.2320311121
• 发表日期: 2024-04-23
• 关键词: spread; responses; invasion; brain; cells; entry

摘要

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 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 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.