Baicalein Inhibits Stx1 and 2 of EHE: Effects of Baicalein on the Cytotoxicity, Production, and Secretion of Shiga Toxins of Enterohaemorrhagic Escherichia coli.

Vinh Vinh,Masuda Masuda,Miyamoto Miyamoto,Nakayama Nakayama,Yamada Yamada,Sato Sato,Duc Duc,Ozawa Ozawa,Honjoh Honjoh,Shinohara Shinohara

doi:10.3390/toxins11090505

Vinh Vinh, Masuda Masuda + Show 8 more

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https://doi.org/10.3390/toxins11090505

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Journal: Toxins	Publication Date: Aug 29, 2019
Citations: 12	License type: CC BY 4.0

Affiliation: Kyushu University, Kao Corporation (Japan)

Abstract

Shiga toxin-producing enterohaemorrhagic Escherichia coli (EHEC) O157:H7 is an important foodborne pathogen. Baicalein (5,6,7-trihydroxylflavone), a flavone isolated from the roots of Scutellaria baicalensis, is considered as a potential antibacterial agent to control foodborne pathogens. Among seven compounds selected by in silico screening of the natural compound database, baicalein inhibited the cytotoxicity of both Shiga toxins 1 and 2 (Stx1 and Stx2) against Vero cells after pretreatment at 0.13 mmol/L. In addition, baicalein reduced the susceptibility of Vero cells to both Stx1 and Stx2. Real-time qPCR showed that baicalein increased transcription of stx1 but not of stx2. However, baicalein had no effects on production or secretion of Stx1 or Stx2. Docking models suggested that baicalein formed a stable structure with StxB pentamer with low intramolecular energy. The results demonstrate that inhibitory activity of baicalein against the cytotoxicity of both Stx1 and Stx2 might be due to of the formation of a binding structure inside the pocket of the Stx1B and Stx2B pentamers.

Highlights

Enterohaemorrhagic Escherichia coli (EHEC) causes foodborne illness and can lead to haemorrhagic colitis and potentially fatal haemolytic uraemic syndrome (HUS) [1]
In the previous study [16], we showed that the cytotoxicity of Stx1 was reduced by pretreatment with gallocatechin gallate (GCg) and epigallocatechin gallate (EGCg)
Catechins and theaflavin did not inhibit the cytotoxicity of Stx2 [16]. These results suggest that the tertiary structure of gallocatechin, which is from the galloyl group, is important for Stx1 cytotoxicity inhibition

Summary

Introduction

Enterohaemorrhagic Escherichia coli (EHEC) causes foodborne illness and can lead to haemorrhagic colitis (bloody diarrhoea) and potentially fatal haemolytic uraemic syndrome (HUS) [1]. Shiga toxin (Stx) is an important virulence factor of EHEC, known as verocytotoxin or vero toxin. There are two subgroups of Stx, namely Stx and Stx, which are found in different combinations in EHEC isolates [2]. Stx is one of the AB-5 family of toxins, consisting of a pentameric B subunit noncovalently bound to an enzymatically active A subunit. The Stx receptors are glycolipids of the globo-series, of which globotriaosylceramides (Gb3s) is the primary receptor found on the surface of vascular endothelial cells and kidney epithelial cells. Stx subtypes have been shown to bind with different affinities to multiple glycolipid receptors.

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