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

Affiliation

Lee SJ(#)(1), You JS(#)(2), Gharbi A(#)(3), Kim YJ(3), Lee MS(3), Kim DH(4)(5), Lee KW(4)(5), Jung ID(6), Park YM(7)(8).
Author information:
(1)Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju, Seoul, 380-701, Republic of Korea.
(2)Department of Biochemistry, School of Medicine, Konkuk University, Chungju, Seoul, 380-701, Republic of Korea.
(3)Dandi Bioscience Inc, 6Th Floor of Real Company, 66, Acha San-ro, Seongdong-gu, Seoul, Republic of Korea.
(4)Division of Life Science, Research Institute of Natural Science
(RINS), Gyeongsang National University
(GNU), 501 Jinju-daero, Jinju, 52828, Republic of Korea.
(5)Division of Applied Life Science
(BK21 Plus), Research Institute of Natural Science
(RINS), Gyeongsang National University
(GNU), 501 Jinju-daero, Jinju, 52828, Republic of Korea.
(6)Dandi Bioscience Inc, 6Th Floor of Real Company, 66, Acha San-ro, Seongdong-gu, Seoul, Republic of Korea. [Email]
(7)Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju, Seoul, 380-701, Republic of Korea. [Email]
(8)Dandi Bioscience Inc, 6Th Floor of Real Company, 66, Acha San-ro, Seongdong-gu, Seoul, Republic of Korea. [Email]
(#)Contributed equally

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.