TY - JOUR
T1 - An organogold compound as potential antimicrobial agent against drug resistant bacteria
T2 - Initial mechanistic insights
AU - Chakraborty, Parichita
AU - Oosterhuis, Dorenda
AU - Bonsignore, Riccardo
AU - Casini, Angela
AU - Olinga, Peter
AU - Scheffers, Dirk-Jan
N1 - © 2021 Wiley-VCH GmbH.
PY - 2021/10/6
Y1 - 2021/10/6
N2 - 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.
AB - 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.
U2 - 10.1002/cmdc.202100342
DO - 10.1002/cmdc.202100342
M3 - Article
C2 - 34181818
SN - 1860-7179
VL - 16
SP - 3060
EP - 3070
JO - ChemMedChem
JF - ChemMedChem
IS - 19
ER -