An Organogold Compound as Potential Antimicrobial Agent against Drug-Resistant Bacteria: Initial Mechanistic Insights

Parichita Chakraborty, Dorenda Oosterhuis, Riccardo Bonsignore, Angela Casini, Peter Olinga, Dirk Jan Scheffers

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The rise of antimicrobial resistance has necessitated novel strategies to efficiently combat pathogenic bacteria. Metal-based compounds have been proven as a possible alternative to classical organic drugs. Here, we have assessed the antibacterial activity of seven gold complexes of different families. One compound, a cyclometalated Au(III) C^N complex, showed activity against Gram-positive bacteria, including multi-drug resistant clinical strains. The mechanism of action of this compound was studied in Bacillus subtilis. Overall, the studies point towards a complex mode of antibacterial action, which does not include induction of oxidative stress or cell membrane damage. A number of genes related to metal transport and homeostasis were upregulated upon short treatment of the cells with gold compound. Toxicity tests conducted on precision-cut mouse tissue slices ex vivo revealed that the organogold compound is poorly toxic to mouse liver and kidney tissues, and may thus, be treated as an antibacterial drug candidate.

Original languageEnglish
Pages (from-to)3060-3070
Number of pages11
JournalChemMedChem
Volume16
Issue number19
DOIs
StatePublished - 6 Oct 2021

Keywords

  • Antibiotics
  • drug resistant bacteria
  • gold compounds
  • mode of action.
  • organometallic drugs

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