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    Area of Science:

    • Microbiology
    • Cancer Research
    • Systems Biology

    Background:

    • Bacterial colonization of tumors is common, but the dynamics of this process are poorly understood.
    • Intratumor bacteria have clinical significance, yet colonization dynamics require further investigation.

    Purpose of the Study:

    • To investigate the population dynamics of bacterial colonization within murine tumors.
    • To develop a dynamical model for tumor colonization by bacteria.

    Main Methods:

    • Genetically barcoded Escherichia coli were introduced into murine tumors via intravenous and intratumor injections.
    • Barcode sequencing was used to track bacterial populations and diversity in resected tumors.
    • Mathematical modeling was employed to analyze bacterial growth patterns and constraints.

    Main Results:

    • Intravenous injection led to narrow infection bottlenecks followed by rapid, nonuniform bacterial growth.
    • Bacteria reached a steady state within a day, maintaining load and diversity.
    • Intratumor injection revealed bacterial progeny sizes following a scale-free distribution (Zipf's law).

    Conclusions:

    • Bacterial tumor colonization is characterized by bottlenecks and constrained growth dynamics.
    • A model incorporating local niche, global resource competition, and noise explains observed dynamics.
    • Descriptive statistics can help differentiate true tumor microbiomes from contamination.