6533b863fe1ef96bd12c77e6

RESEARCH PRODUCT

An organogold compound as potential antimicrobial agent against drug resistant bacteria: Initial mechanistic insights

Angela CasiniDorenda OosterhuisDirk-jan ScheffersRiccardo BonsignorePeter OlingaParichita Chakraborty

subject

Cell Survivalmedicine.drug_classAntibioticsorganometallic drugsmode of action.Microbial Sensitivity TestsGram-Positive Bacteriamedicine.disease_causeBiochemistrydrug resistant bacteriaMiceStructure-Activity RelationshipAntibioticsDrug Discoverygold compoundsmedicineAnimalsGeneral Pharmacology Toxicology and PharmaceuticsMode of actionPharmacologyFull PaperDose-Response Relationship DrugMolecular StructurebiologyChemistryOrganic ChemistryPathogenic bacteriaFull Papersbiology.organism_classificationAntimicrobialAnti-Bacterial AgentsMechanism of actionBiochemistryMolecular Medicinemedicine.symptomAntibacterial activityOrganogold CompoundsBacteriaEx vivo

description

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.

10.1002/cmdc.202100342https://research.rug.nl/en/publications/22b06f16-0384-4714-8bef-f33143b8710e