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Operation of Laboratory Photobioreactors with Online Growth Measurements and Customizable Light Regimes

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Oxygen concentration modulates colibactin production.

Nadège Bossuet¹, Cécile Guyonnet¹, Camille V Chagneau^1,2

¹IRSD, Université de Toulouse, INSERM, INRAE, ENVT, Univ Toulouse III Paul Sabatier (UPS), Toulouse, France.

|June 14, 2023

Summary

Colibactin, a genotoxic metabolite produced by E. coli, is synthesized maximally under anoxic conditions. Its production is regulated by aerobic respiration control (ArcA) and inhibited by oxygen, suggesting adaptation to the gut lumen.

Keywords:

DNA damage Escherichia coli colibactin hypoxia oxygen

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Area of Science:

Microbiology
Molecular Biology
Cancer Research

Background:

Up to 25% of human E. coli strains carry the pks genomic island, which encodes colibactin synthesis.
Colibactin is a genotoxic metabolite implicated in colorectal cancer development.
The intestinal environment features a steep oxygen gradient, from hypoxic epithelial surfaces to anaerobic lumens.

Purpose of the Study:

To investigate the conditions influencing colibactin production in the gut.
To determine the role of oxygen availability in colibactin synthesis.
To elucidate the regulatory mechanisms controlling colibactin expression.

Main Methods:

Culturing pks+ E. coli under varying oxygen concentrations.
Measuring colibactin production and genotoxicity.
Analyzing the role of the aerobic respiration control (ArcA) system.

Main Results:

Colibactin production is highest under anoxic conditions and decreases with increasing oxygen levels.
Aerobic respiration control (ArcA) positively regulates colibactin production and genotoxicity in response to oxygen.
Oxygen inhibits the pks biosynthetic pathway.

Conclusions:

Colibactin synthesis is adapted to the anoxic intestinal lumen.
The pks pathway is regulated by oxygen availability, favoring production in hypoxic or anoxic environments.
Understanding colibactin regulation is crucial for its role in colorectal cancer.