The Infectious Dose Shapes Vibrio cholerae Within-Host Dynamics.

Area of Science:

• Microbiology and Infectious Diseases
• Population Dynamics
• Mathematical Modeling

Background:

• Understanding bacterial population dynamics (replication, death, migration) is crucial for predicting infection progression and evolution.
• Quantifying these rates simultaneously within a host presents significant methodological challenges.

Purpose of the Study:

• To disentangle and continuously measure the rates of replication, death, and migration of Vibrio cholerae within a host.
• To investigate the impact of inoculum size on bacterial population dynamics and niche availability.
• To develop a predictive model for within-host bacterial spatiotemporal dynamics.

Main Methods:

• Utilized a mouse model and uniquely tagged individual Vibrio cholerae bacteria (>500 fitness-neutral genomic tags).
• Employed next-generation sequencing to track changes in tag frequencies and quantify bacterial populations (CFU).
• Integrated tag frequency data and CFU counts into a mathematical model to infer population dynamic rates.

Main Results:

• Demonstrated substantial spatiotemporal heterogeneity in Vibrio cholerae replication, death, and migration rates along the mouse gastrointestinal tract.
• Showed that the available niche for Vibrio cholerae increases with the inoculum size, indicating potential cooperative effects.
• The developed mathematical model exhibited robust predictive power across different experimental conditions.

Conclusions:

• Bacterial population dynamics within a host are complex and spatially heterogeneous, influenced by factors beyond simple exposure likelihood.
• Inoculum size significantly impacts pathogen burden and niche expansion, highlighting the importance of dose-response relationships in disease.
• This approach provides a powerful framework for dissecting microbial population dynamics during infection.