The Infectious Dose Shapes Vibrio cholerae Within-Host Dynamics

Aaron Nicholas Gillman, Anel Mahmutovic, Pia Abel zur Wiesch, Sören Abel

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

During infection, the rates of pathogen replication, death, and migration affect disease progression, dissemination, transmission, and resistance evolution. Here, we follow the population dynamics of Vibrio cholerae in a mouse model by labeling individual bacteria with one of .500 unique, fitness-neutral genomic tags. Using the changes in tag frequencies and CFU numbers, we inform a mathematical model that describes the within-host spatiotemporal bacterial dynamics. This allows us to disentangle growth, death, forward, and retrograde migration rates continuously during infection. Our model has robust predictive power across various experimental setups. The population dynamics of V. cholerae shows substantial spatiotemporal heterogeneity in replication, death, and migration. Importantly, we find that the niche available to V. cholerae in the host increases with inoculum size, suggesting cooperative effects during infection. Therefore, it is not enough to consider just the likelihood of exposure (50% infectious dose) but rather the magnitude of exposure to predict outbreaks.

Original languageEnglish (US)
Article numbere00659-21
JournalmSystems
Volume6
Issue number6
DOIs
StatePublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Physiology
  • Biochemistry
  • Computer Science Applications
  • Microbiology
  • Modeling and Simulation

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