Artemisinin displays bactericidal activity via copper-mediated DNA damage

Virulence. 2022 Dec;13(1):149-159. doi: 10.1080/21505594.2021.2021643.

Abstract

Artemisinin (ARS) and its semi-synthetic derivatives are effective drugs to treat malaria and possess multiple therapeutic activities based on their endoperoxide bridge. Here, we showed that ARS displayed antibacterial efficacy in Drosophila systemic infections caused by bacterial pathogens but killed only Vibrio cholerae (VC) in vitro, involving reactive oxygen species (ROS) generation and/or DNA damage. This selective antibacterial activity of ARS was attributed to the higher intracellular copper levels in VC, in that the antibacterial activity was observed in vitro upon addition of cuprous ions even against other bacteria and was compromised by the copper-specific chelators neocuproine (NC) and triethylenetetramine (TETA) in vitro and in vivo. We suggest that copper can enhance or reinforce the therapeutic activities of ARS to be repurposed as an antibacterial drug for the treatment of bacterial infections.

Keywords: Artemisinin; Vibrio cholerae; antibacterial; antimalarial; copper.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Artemisinins* / pharmacology
  • Copper* / pharmacology
  • DNA Damage

Substances

  • Anti-Bacterial Agents
  • Artemisinins
  • Copper
  • artemisinin