Artemisinin displays bactericidal activity via copper-mediated DNA damage

Area of Science:

• Pharmacology
• Microbiology
• Biochemistry

Background:

• Artemisinin (ARS) and its derivatives are established antimalarial drugs with diverse therapeutic properties.
• Their efficacy stems from the unique endoperoxide bridge structure.
• ARS has demonstrated potential beyond malaria treatment.

Purpose of the Study:

• To investigate the antibacterial activity of Artemisinin (ARS).
• To elucidate the mechanism behind ARS's selective antibacterial action.
• To explore the potential of ARS as an antibacterial agent, possibly in combination with copper.

Main Methods:

• In vitro testing of ARS against bacterial pathogens, including Vibrio cholerae (VC).
• Assessment of reactive oxygen species (ROS) generation and DNA damage.
• In vitro and in vivo experiments involving copper ions, cuprous ions, and copper-specific chelators (neocuproine, triethylenetetramine).
• Drosophila systemic infection models were used.

Main Results:

• ARS exhibited antibacterial efficacy in Drosophila but selectively killed Vibrio cholerae in vitro.
• The selective activity was linked to higher intracellular copper levels in VC.
• Addition of cuprous ions enhanced ARS antibacterial activity against other bacteria in vitro.
• Copper-specific chelators diminished ARS activity both in vitro and in vivo.

Conclusions:

• Copper plays a crucial role in potentiating the antibacterial activity of Artemisinin.
• ARS demonstrates selective antibacterial properties influenced by intracellular copper concentrations.
• Copper can enhance ARS efficacy, suggesting a potential repurposing strategy for treating bacterial infections.