Faced with the toxic threat of copper, bacteria have developed remarkable detoxification strategies. One of these relies on the enzyme CueO. A team of scientists in Marseille has highlighted the key role of specific domains of these enzymes that act as true molecular antennas in managing and eliminating excess copper.
These findings, published in
PNAS, could lead to numerous biotechnological and therapeutic applications.
Copper, while essential for many biological processes, becomes toxic when it accumulates in cells. To protect themselves, bacteria such as
Escherichia coli use sophisticated detoxification systems.
One of these systems involves the enzyme CueO. This multicopper oxidase transforms copper ions (Cu
+) into a less harmful form (Cu
2+), while minimizing the formation of destructive oxygen radicals. An intriguing feature of the CueO enzyme is its flexible, methionine-rich domain, the function of which remains largely debated.
A team of chemists and biologists from the Bioenergetics and Protein Engineering laboratory and the Bacterial Chemistry Laboratory (CNRS/Aix Marseille University) investigated the role of this domain by combining biochemical, biophysical, and electrochemical experiments with tests on live bacteria.
They discovered that it acts as a true copper collector, facilitating the access of Cu
+ ions tightly bound to other molecules to the enzyme's active site, thereby accelerating their transformation.
This study, published in
PNAS, opens up promising prospects for therapeutic and biotechnological innovations. On one hand, understanding these bacterial detoxification mechanisms could inspire biotechnologies that leverage the ability of enzymes to manipulate copper. On the other hand, copper is one of the weapons used by macrophages to combat bacterial infections.
This understanding could shed light on how pathogens such as
Escherichia,
Pseudomonas, or
Salmonella evade the immune system and inspire the development of innovative therapies to combat antibiotic resistance—a promising avenue in the fight against pathogenic bacteria.
Author: AVR
Reference:
Methionine-rich domains emerge as facilitators of copper recruitment in detoxification systems
PNAS 2024
https://doi.org/10.1073/pnas.240286212