# Bacterial population dynamics during colonization of solid tumors

**Authors:** Serkan Sayin, Motasem ElGamel, Brittany Rosener, Michael Brehm, Andrew Mugler, Amir Mitchell

PMC · DOI: 10.1038/s44320-025-00175-5 · Molecular Systems Biology · 2025-12-15

## TL;DR

This study explores how bacteria colonize tumors in mice, revealing patterns of bacterial growth and diversity within tumors.

## Contribution

The paper introduces the first dynamical model of bacterial tumor colonization and identifies key colonization mechanisms.

## Key findings

- Tumor colonization begins with a narrow bottleneck followed by rapid, uneven bacterial growth.
- Bacterial progeny sizes follow a scale-free distribution when injected directly into tumors.
- A growth model incorporating local niche load, global resource competition, and noise explains the observed dynamics.

## Abstract

Bacterial colonization of tumors is widespread, yet the dynamics during colonization remain underexplored. Here we discover strong variability in the sizes of intratumor bacterial clones and use this variability to infer the mechanisms of colonization. We monitored bacterial population dynamics in murine tumors after introducing millions of genetically barcoded Escherichia coli cells. Results from intravenous injection revealed that roughly a hundred bacteria seeded a tumor and that colonizers underwent rapid, yet highly nonuniform growth. Within a day, bacteria reached a steady-state and then sustained load and clone diversity. Intratumor injections, circumventing colonization bottlenecks, revealed that the nonuniformity persists and that the sizes of bacterial progenies followed a scale-free distribution. Theory suggested that our observations are compatible with a growth model constrained by a local niche load, global resource competition, and noise. Our work provides the first dynamical model of tumor colonization and may allow distinguishing genuine tumor microbiomes from contamination.

Bacterial population dynamics were monitored during cancer tumor colonization using a mouse model system. A combined experimental and theoretical approach inferred the key processes driving bacterial colonization and provided the first dynamical model of tumor colonization.

Colonization after intravenous injection revealed that tumor colonization is governed by a narrow bottleneck followed by rapid uneven growth of colonizers.Colonization after intratumor injection, circumventing the colonization bottleneck, revealed that the nonuniformity persists and that the sizes of bacterial progenies follow a scale-free distribution matching Zipf’s law.Theory suggested that observations are compatible with a growth model constrained by a local niche load, global resource competition, and noise.

Colonization after intravenous injection revealed that tumor colonization is governed by a narrow bottleneck followed by rapid uneven growth of colonizers.

Colonization after intratumor injection, circumventing the colonization bottleneck, revealed that the nonuniformity persists and that the sizes of bacterial progenies follow a scale-free distribution matching Zipf’s law.

Theory suggested that observations are compatible with a growth model constrained by a local niche load, global resource competition, and noise.

Bacterial population dynamics were monitored during cancer tumor colonization using a mouse model system. A combined experimental and theoretical approach inferred the key processes driving bacterial colonization and provided the first dynamical model of tumor colonization.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)
- **Species:** Escherichia coli (taxon 562), Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** solid tumors (MESH:D009369)
- **Species:** Escherichia coli (E. coli, species) [taxon 562], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12953616/full.md

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Source: https://tomesphere.com/paper/PMC12953616