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Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes

Hydroquinine has antimicrobial potential with demonstrated activity against several bacteria, including multidrug-resistant (MDR) P. aeruginosa reference strains. Despite this, there is limited evidence confirming the antibacterial activity of hydroquinine against clinical isolates and the underlyin...

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Autores principales: Weawsiangsang, Sattaporn, Rattanachak, Nontaporn, Jongjitvimol, Touchkanin, Jaifoo, Theerasak, Charoensit, Pensri, Viyoch, Jarupa, Ross, Sukunya, Ross, Gareth M., Baldock, Robert A., Jongjitwimol, Jirapas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530414/
https://www.ncbi.nlm.nih.gov/pubmed/37762218
http://dx.doi.org/10.3390/ijms241813914
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author Weawsiangsang, Sattaporn
Rattanachak, Nontaporn
Jongjitvimol, Touchkanin
Jaifoo, Theerasak
Charoensit, Pensri
Viyoch, Jarupa
Ross, Sukunya
Ross, Gareth M.
Baldock, Robert A.
Jongjitwimol, Jirapas
author_facet Weawsiangsang, Sattaporn
Rattanachak, Nontaporn
Jongjitvimol, Touchkanin
Jaifoo, Theerasak
Charoensit, Pensri
Viyoch, Jarupa
Ross, Sukunya
Ross, Gareth M.
Baldock, Robert A.
Jongjitwimol, Jirapas
author_sort Weawsiangsang, Sattaporn
collection PubMed
description Hydroquinine has antimicrobial potential with demonstrated activity against several bacteria, including multidrug-resistant (MDR) P. aeruginosa reference strains. Despite this, there is limited evidence confirming the antibacterial activity of hydroquinine against clinical isolates and the underlying mechanism of action. Here, we aimed to investigate the antibacterial effect of hydroquinine in clinical P. aeruginosa strains using phenotypic antimicrobial susceptibility testing and synergistic testing. In addition, we examined the potential inhibitory mechanisms against MDR P. aeruginosa isolates using informatic-driven molecular docking analysis in combination with RT-qPCR. We uncovered that hydroquinine inhibits and kills clinical P. aeruginosa at 2.50 mg/mL (MIC) and 5.00 mg/mL (MBC), respectively. Hydroquinine also showed partial synergistic effects with ceftazidime against clinical MDR P. aeruginosa strains. Using SwissDock, we identified potential interactions between arginine deiminase (ADI)-pathway-related proteins and hydroquinine. Furthermore, using RT-qPCR, we found that hydroquinine directly affects the mRNA expression of arc operon. We demonstrated that the ADI-related genes, including the arginine/ornithine antiporter (arcD) and the three enzymes (arginine deiminase (arcA), ornithine transcarbamylase (arcB), and carbamate kinase (arcC)), were significantly downregulated at a half MIC of hydroquinine. This study is the first report that the ADI-related proteins are potential molecular targets for the inhibitory effect of hydroquinine against clinically isolated MDR P. aeruginosa strains.
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spelling pubmed-105304142023-09-28 Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes Weawsiangsang, Sattaporn Rattanachak, Nontaporn Jongjitvimol, Touchkanin Jaifoo, Theerasak Charoensit, Pensri Viyoch, Jarupa Ross, Sukunya Ross, Gareth M. Baldock, Robert A. Jongjitwimol, Jirapas Int J Mol Sci Article Hydroquinine has antimicrobial potential with demonstrated activity against several bacteria, including multidrug-resistant (MDR) P. aeruginosa reference strains. Despite this, there is limited evidence confirming the antibacterial activity of hydroquinine against clinical isolates and the underlying mechanism of action. Here, we aimed to investigate the antibacterial effect of hydroquinine in clinical P. aeruginosa strains using phenotypic antimicrobial susceptibility testing and synergistic testing. In addition, we examined the potential inhibitory mechanisms against MDR P. aeruginosa isolates using informatic-driven molecular docking analysis in combination with RT-qPCR. We uncovered that hydroquinine inhibits and kills clinical P. aeruginosa at 2.50 mg/mL (MIC) and 5.00 mg/mL (MBC), respectively. Hydroquinine also showed partial synergistic effects with ceftazidime against clinical MDR P. aeruginosa strains. Using SwissDock, we identified potential interactions between arginine deiminase (ADI)-pathway-related proteins and hydroquinine. Furthermore, using RT-qPCR, we found that hydroquinine directly affects the mRNA expression of arc operon. We demonstrated that the ADI-related genes, including the arginine/ornithine antiporter (arcD) and the three enzymes (arginine deiminase (arcA), ornithine transcarbamylase (arcB), and carbamate kinase (arcC)), were significantly downregulated at a half MIC of hydroquinine. This study is the first report that the ADI-related proteins are potential molecular targets for the inhibitory effect of hydroquinine against clinically isolated MDR P. aeruginosa strains. MDPI 2023-09-10 /pmc/articles/PMC10530414/ /pubmed/37762218 http://dx.doi.org/10.3390/ijms241813914 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Weawsiangsang, Sattaporn
Rattanachak, Nontaporn
Jongjitvimol, Touchkanin
Jaifoo, Theerasak
Charoensit, Pensri
Viyoch, Jarupa
Ross, Sukunya
Ross, Gareth M.
Baldock, Robert A.
Jongjitwimol, Jirapas
Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes
title Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes
title_full Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes
title_fullStr Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes
title_full_unstemmed Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes
title_short Hydroquinine Inhibits the Growth of Multidrug-Resistant Pseudomonas aeruginosa via the Suppression of the Arginine Deiminase Pathway Genes
title_sort hydroquinine inhibits the growth of multidrug-resistant pseudomonas aeruginosa via the suppression of the arginine deiminase pathway genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530414/
https://www.ncbi.nlm.nih.gov/pubmed/37762218
http://dx.doi.org/10.3390/ijms241813914
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