Less is more: Enterobactin concentration dependency in copper tolerance and toxicity

Area of Science:

• Microbiology
• Biochemistry
• Toxicology

Background:

• Siderophores, beyond iron acquisition, have diverse cellular roles.
• Enterobactin previously shown to increase copper toxicity by reducing Cu2+ to Cu+.
• Copper toxicity involves reactive oxygen species (ROS) and enzyme mismetallation.

Purpose of the Study:

• Investigate the dual role of enterobactin in copper toxicity.
• Determine the concentration-dependent effects of enterobactin on copper toxicity.
• Elucidate the mechanisms underlying enterobactin's protective and harmful effects.

Main Methods:

• Utilized Escherichia coli (E. coli) as a model organism.
• Assessed cellular sensitivity to copper under varying enterobactin concentrations.
• Measured reactive oxygen species (ROS) levels.
• Investigated enterobactin uptake and hydrolysis within cells.
• Analyzed enterobactin gene expression in response to copper and oxygen.

Main Results:

• Enterobactin absence increased E. coli sensitivity to copper-induced ROS.
• Low enterobactin concentrations reduced ROS, conferring protection.
• Enterobactin protection required cellular uptake and cytoplasmic hydrolysis.
• Copper and oxygen induced enterobactin expression.
• Copper counteracted iron's downregulation of enterobactin synthesis.
• High enterobactin concentrations exacerbated copper toxicity, likely via Cu2+ reduction.

Conclusions:

• Enterobactin displays a bimodal effect on copper toxicity, acting protectively at low concentrations and harmfully at high concentrations.
• The protective effect is linked to ROS mitigation, dependent on enterobactin internalization and hydrolysis.
• High enterobactin levels enhance copper toxicity, posing a significant risk to E. coli.