An Organogold Compound As Potential Antimicrobial Agent Against Drug-Resistant Bacteria: Initial Mechanistic Insights

Overview

Journal ChemMedChem

Specialties Chemistry
Pharmacology

Date 2021 Jun 28

PMID 34181818

Citations 14

Authors

Parichita Chakraborty

Dorenda Oosterhuis

Riccardo Bonsignore

Angela Casini

Peter Olinga

Dirk-Jan Scheffers

Affiliations

Soon will be listed here.

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.

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