Copper Induces Protein Aggregation, a Toxic Process Compensated by Molecular Chaperones

Area of Science:

• Microbiology
• Biochemistry
• Molecular Biology

Background:

• Copper exhibits antimicrobial and antiviral properties, with toxicity often linked to reactive oxygen species (ROS) under aerobic conditions.
• Copper toxicity is significantly higher under anaerobic conditions, where ROS production is absent, suggesting alternative toxicity mechanisms.
• The precise molecular mechanisms of copper toxicity, particularly under anaerobic conditions, remain incompletely understood.

Purpose of the Study:

• To investigate the mechanism of copper toxicity in bacteria under anaerobic conditions.
• To identify the role of protein aggregation in copper-induced cell death.
• To elucidate the bacterial defense mechanisms against copper stress.

Main Methods:

• Treatment of Escherichia coli with copper (Cu+) under anaerobic conditions.
• In vitro experiments using E. coli lysates to assess protein aggregation.
• Proteomic analysis of aggregated proteins to identify key residues involved.
• Assessment of copper sensitivity in E. coli strains lacking specific molecular chaperones (DnaK, trigger factor).

Main Results:

• Copper treatment under anaerobic conditions significantly increases protein aggregation in E. coli, independent of ROS.
• Cu+ directly induces protein aggregation in vitro, with a preference for proteins containing cysteine and histidine residues.
• Bacterial strains deficient in cytosolic chaperones DnaK or trigger factor exhibit heightened sensitivity to copper stress.
• These chaperones play a crucial role in protecting bacteria against copper-induced protein aggregation and cell death.

Conclusions:

• Copper toxicity under anaerobic conditions is primarily mediated by ROS-independent protein aggregation.
• Copper (Cu+) interacts non-specifically with cysteine and histidine residues, leading to widespread protein aggregation.
• Molecular chaperones DnaK and trigger factor are essential for bacterial survival under copper stress by preventing protein aggregation.
• Understanding copper-induced protein aggregation provides insights into novel antibacterial strategies and bacterial defense mechanisms.