Inhibition of Shiga toxin-converting bacteriophage development by novel antioxidant compounds

Sylwia Bloch , Bożena Nejman-Faleńczyk , Karolina Pierzynowska , Ewa Piotrowska , Alicja Węgrzyn , Christelle Marminon , Zouhair Bouaziz , Pascal Nebois , Joachim Jose , Marc Le Borgne , Luciano Saso , Grzegorz Węgrzyn

Abstract

Oxidative stress may be the major cause of induction of Shiga toxin-converting (Stx) prophages from chromosomes of Shiga toxin-producing Escherichia coli (STEC) in human intestine. Thus, we aimed to test a series of novel antioxidant compounds for their activities against prophage induction, thus, preventing pathogenicity of STEC. Forty-six compounds (derivatives of carbazole, indazole, triazole, quinolone, ninhydrine, and indenoindole) were tested. Fifteen of them gave promising results and were further characterized. Eleven compounds had acceptable profiles in cytotoxicity tests with human HEK-293 and HDFa cell lines. Three of them (selected for molecular studies) prevent the prophage induction at the level of expres- sion of specific phage genes. In bacterial cells treated with hydrogen peroxide, expression of genes involved in the oxidative stress response was significantly less efficient in the presence of the tested compounds. Therefore, they apparently reduce the oxidative stress, which prevents induction of Stx prophage in E. coli.
Author Sylwia Bloch (FB / DMoB)
Sylwia Bloch,,
- Department of Molecular Biology
, Bożena Nejman-Faleńczyk (FB / DMoB)
Bożena Nejman-Faleńczyk,,
- Department of Molecular Biology
, Karolina Pierzynowska (FB / DMoB)
Karolina Pierzynowska,,
- Department of Molecular Biology
, Ewa Piotrowska (FB / DMoB)
Ewa Piotrowska,,
- Department of Molecular Biology
, Alicja Węgrzyn - [Institute of Biochemistry and Biophysics of the Polish Academy of Sciences]
Alicja Węgrzyn,,
-
- Institute of Biochemistry and Biophysics of the Polish Academy of Sciences
, Christelle Marminon - [Biomolécules, Cancer et Chimiorésistances]
Christelle Marminon,,
-
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, Zouhair Bouaziz - [Biomolécules, Cancer et Chimiorésistances]
Zouhair Bouaziz,,
-
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, Pascal Nebois - [Biomolécules, Cancer et Chimiorésistances]
Pascal Nebois,,
-
-
, Joachim Jose - [Westfälische Wilhelms-Universität Münster]
Joachim Jose,,
-
-
, Marc Le Borgne - [Biomolécules, Cancer et Chimiorésistances]
Marc Le Borgne,,
-
-
et al.`
Journal seriesJournal of Enzyme Inhibition and Medicinal Chemistry, ISSN 1475-6366, (A 25 pkt)
Issue year2018
Vol33
No1
Pages639-650
Publication size in sheets0.55
Keywords in EnglishShiga toxin-producing, Escherichia coli, Shiga toxin-converting bacteriophage, oxidative stress, antioxidants, heterocyclic compounds
ASJC Classification3002 Drug Discovery; 3004 Pharmacology; 2700 General Medicine
DOIDOI:10.1080/14756366.2018.1444610
URL https://www.tandfonline.com/doi/pdf/10.1080/14756366.2018.1444610?needAccess=true
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)25
ScoreMinisterial score = 25.0, 10-09-2019, ArticleFromJournal
Publication indicators WoS Citations = 0; Scopus Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.847; WoS Impact Factor: 2017 = 3.638 (2) - 2017=3.0 (5)
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