Colibactin leads to a bacteria-specific mutation pattern and self-inflicted DNA damage Original paper

What was studied?

This study tested whether the microbiome genotoxin colibactin harms bacteria and whether it leaves a distinct mutation pattern in bacterial genomes. The authors combined coculture killing experiments, a genome-wide knockout sensitivity screen, and mutation-accumulation whole-genome sequencing to connect colibactin exposure to bacterial death, DNA repair dependence, and specific mutational outcomes.

Who was studied?

The “subjects” were bacterial strains, mainly Escherichia coli. The team exposed an ampicillin-resistant E. coli target strain to engineered pks-positive producer strains or pks-negative controls, screened a pooled E. coli knockout library to find genes that protect against colibactin toxicity, and tested self-damage in producing backgrounds including the naturally producing probiotic E. coli Nissle 1917.

What were the most important findings?

Colibactin directly damaged bacteria in a contact-dependent way: producer strains reduced the survival of neighboring E. coli, and toxicity intensified when conditions favored close contact and stress. The knockout screen showed that survival depended strongly on DNA damage response and homologous recombination pathways (a signal that colibactin creates lesions that require high-fidelity repair), and sequencing demonstrated a clear bacteria-specific mutation signature with a large rise in single-base substitutions that clustered in A/T-rich motifs. Notably, the dominant bacterial signature differed from the mammalian one, suggesting that bacterial repair processing shapes the final mutation pattern, and the study also showed that producing strains experience self-inflicted DNA damage despite resistance mechanisms, implying long-term evolutionary pressure within pks-positive lineages.

What are the greatest implications of this study/ review?

This work expands colibactin from a host-focused carcinogenic factor to a microbiome ecology driver that can kill competitors, trigger DNA repair stress, induce prophage-related effects, and reshape community dynamics through mutagenesis. Clinically and for microbiome signatures, it supports treating pks-positive E. coli (especially B2-associated lineages) as a functional risk feature because these strains can influence both microbial community stability and host-relevant exposures, and it suggests that tracking a bacterial mutation footprint over time could become a way to infer colibactin activity in vivo rather than relying on gene presence alone.