IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria

Abstract Sepsis is caused by organ dysfunction initiated by an unrestrained host immune response to infection. The emergence of antibiotic-resistant bacteria has rapidly increased in the last decades and has stimulated a firm research platform to combat infections caused by antibiotic-resistant bact...

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Main Authors:	Su Jin Lee, Jueng Soo You, Amal Gharbi, Yong Joo Kim, Mi Suk Lee, Dong Hwan Kim, Keun Woo Lee, In Duk Jung, Yeong Min Park
Format:	article
Language:	EN
Published:	Nature Portfolio 2021
Subjects:	Medicine R Science Q
Online Access:	https://doaj.org/article/f2408c62fcc84bdaaaea1ace308d3416
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spelling	oai:doaj.org-article:f2408c62fcc84bdaaaea1ace308d34162021-12-02T10:44:08ZIOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria10.1038/s41598-021-82377-z2045-2322https://doaj.org/article/f2408c62fcc84bdaaaea1ace308d34162021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82377-zhttps://doaj.org/toc/2045-2322Abstract Sepsis is caused by organ dysfunction initiated by an unrestrained host immune response to infection. The emergence of antibiotic-resistant bacteria has rapidly increased in the last decades and has stimulated a firm research platform to combat infections caused by antibiotic-resistant bacteria that cannot be eradicated with conventional antibiotics. Strategies like epigenetic regulators such as lysine demethylase (Kdm) has received attention as a new target. Thus, we sought to investigate the epigenetic mechanisms in sepsis pathophysiology with the aim of discovering new concepts for treatment. A transcriptome analysis of dendritic cells during their inflammatory state identified Kdm as a critical molecule in sepsis regulation. Next, 8-hydroxyquinoline-5-carboxylic acid (IOX1) ability to control endotoxemia induced by Lipopolysaccharide and bacterial sepsis was demonstrated. IOX1 has been shown to regulate endotoxemia and sepsis caused by Escherichia coli and carbapenem-resistant Acinetobacter baumannii and has also contributed to the suppression of multidrug-resistant bacterial growth through the inhibition of DNA Gyrase. These findings show that IOX1 could be a component agent against bacterial sepsis by functioning as a broad-spectrum antibiotic with dual effects.Su Jin LeeJueng Soo YouAmal GharbiYong Joo KimMi Suk LeeDong Hwan KimKeun Woo LeeIn Duk JungYeong Min ParkNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Su Jin Lee Jueng Soo You Amal Gharbi Yong Joo Kim Mi Suk Lee Dong Hwan Kim Keun Woo Lee In Duk Jung Yeong Min Park IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria
description	Abstract Sepsis is caused by organ dysfunction initiated by an unrestrained host immune response to infection. The emergence of antibiotic-resistant bacteria has rapidly increased in the last decades and has stimulated a firm research platform to combat infections caused by antibiotic-resistant bacteria that cannot be eradicated with conventional antibiotics. Strategies like epigenetic regulators such as lysine demethylase (Kdm) has received attention as a new target. Thus, we sought to investigate the epigenetic mechanisms in sepsis pathophysiology with the aim of discovering new concepts for treatment. A transcriptome analysis of dendritic cells during their inflammatory state identified Kdm as a critical molecule in sepsis regulation. Next, 8-hydroxyquinoline-5-carboxylic acid (IOX1) ability to control endotoxemia induced by Lipopolysaccharide and bacterial sepsis was demonstrated. IOX1 has been shown to regulate endotoxemia and sepsis caused by Escherichia coli and carbapenem-resistant Acinetobacter baumannii and has also contributed to the suppression of multidrug-resistant bacterial growth through the inhibition of DNA Gyrase. These findings show that IOX1 could be a component agent against bacterial sepsis by functioning as a broad-spectrum antibiotic with dual effects.
format	article
author	Su Jin Lee Jueng Soo You Amal Gharbi Yong Joo Kim Mi Suk Lee Dong Hwan Kim Keun Woo Lee In Duk Jung Yeong Min Park
author_facet	Su Jin Lee Jueng Soo You Amal Gharbi Yong Joo Kim Mi Suk Lee Dong Hwan Kim Keun Woo Lee In Duk Jung Yeong Min Park
author_sort	Su Jin Lee
title	IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria
title_short	IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria
title_full	IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria
title_fullStr	IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria
title_full_unstemmed	IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria
title_sort	iox1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f2408c62fcc84bdaaaea1ace308d3416
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IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria

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