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

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 famili...

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Autores principales: Chakraborty, Parichita, Oosterhuis, Dorenda, Bonsignore, Riccardo, Casini, Angela, Olinga, Peter, Scheffers, Dirk‐Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518660/
https://www.ncbi.nlm.nih.gov/pubmed/34181818
http://dx.doi.org/10.1002/cmdc.202100342
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author Chakraborty, Parichita
Oosterhuis, Dorenda
Bonsignore, Riccardo
Casini, Angela
Olinga, Peter
Scheffers, Dirk‐Jan
author_facet Chakraborty, Parichita
Oosterhuis, Dorenda
Bonsignore, Riccardo
Casini, Angela
Olinga, Peter
Scheffers, Dirk‐Jan
author_sort Chakraborty, Parichita
collection PubMed
description 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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spelling pubmed-85186602021-10-21 An Organogold Compound as Potential Antimicrobial Agent against Drug‐Resistant Bacteria: Initial Mechanistic Insights Chakraborty, Parichita Oosterhuis, Dorenda Bonsignore, Riccardo Casini, Angela Olinga, Peter Scheffers, Dirk‐Jan ChemMedChem Full Papers 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. John Wiley and Sons Inc. 2021-07-23 2021-10-06 /pmc/articles/PMC8518660/ /pubmed/34181818 http://dx.doi.org/10.1002/cmdc.202100342 Text en © 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Chakraborty, Parichita
Oosterhuis, Dorenda
Bonsignore, Riccardo
Casini, Angela
Olinga, Peter
Scheffers, Dirk‐Jan
An Organogold Compound as Potential Antimicrobial Agent against Drug‐Resistant Bacteria: Initial Mechanistic Insights
title An Organogold Compound as Potential Antimicrobial Agent against Drug‐Resistant Bacteria: Initial Mechanistic Insights
title_full An Organogold Compound as Potential Antimicrobial Agent against Drug‐Resistant Bacteria: Initial Mechanistic Insights
title_fullStr An Organogold Compound as Potential Antimicrobial Agent against Drug‐Resistant Bacteria: Initial Mechanistic Insights
title_full_unstemmed An Organogold Compound as Potential Antimicrobial Agent against Drug‐Resistant Bacteria: Initial Mechanistic Insights
title_short An Organogold Compound as Potential Antimicrobial Agent against Drug‐Resistant Bacteria: Initial Mechanistic Insights
title_sort organogold compound as potential antimicrobial agent against drug‐resistant bacteria: initial mechanistic insights
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518660/
https://www.ncbi.nlm.nih.gov/pubmed/34181818
http://dx.doi.org/10.1002/cmdc.202100342
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