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An Organogold Compound as Potential Antimicrobial Agent against Drug‐Resistant Bacteria: Initial Mechanistic Insights
Author(s) -
Chakraborty Parichita,
Oosterhuis Dorenda,
Bonsignore Riccardo,
Casini Angela,
Olinga Peter,
Scheffers DirkJan
Publication year - 2021
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202100342
Subject(s) - antimicrobial , bacillus subtilis , bacteria , antibacterial activity , drug , chemistry , microbiology and biotechnology , drug resistance , in vivo , mechanism of action , mode of action , pharmacology , drug action , biology , biochemistry , in vitro , genetics
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.