The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>

Lytic transglycosylases such as Slt35 from <i>E. coli</i> are enzymes involved in bacterial cell wall remodelling and recycling, which represent potential targets for novel antibacterial agents. Here, we investigated a series of known glycosidase inhibitors for their ability to inhibit S...

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Main Authors:	Aysha B. Mezoughi, Chiara M. Costanzo, Gregor M. Parker, Enas M. Behiry, Alan Scott, Andrew C. Wood, Sarah E. Adams, Richard B. Sessions, E. Joel Loveridge
Format:	Article
Language:	English
Published:	MDPI AG 2021-07-01
Series:	Molecules
Subjects:	lytic transglycosylase thionine acetate enzyme inhibition antibacterial
Online Access:	https://www.mdpi.com/1420-3049/26/14/4189

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spelling	doaj-84b975e7244748d283e024c32655050f2021-07-23T13:56:23ZengMDPI AGMolecules1420-30492021-07-01264189418910.3390/molecules26144189The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>Aysha B. Mezoughi0Chiara M. Costanzo1Gregor M. Parker2Enas M. Behiry3Alan Scott4Andrew C. Wood5Sarah E. Adams6Richard B. Sessions7E. Joel Loveridge8School of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKDepartment of Chemistry, Swansea University, Singleton Park, Swansea SA2 8PP, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKSchool of Biochemistry, University of Bristol, University Walk, Bristol BS8 1TD, UKSchool of Chemistry, Cardiff University, Park Place, Cardiff CF10 3AT, UKLytic transglycosylases such as Slt35 from <i>E. coli</i> are enzymes involved in bacterial cell wall remodelling and recycling, which represent potential targets for novel antibacterial agents. Here, we investigated a series of known glycosidase inhibitors for their ability to inhibit Slt35. While glycosidase inhibitors such as 1-deoxynojirimycin, castanospermine, thiamet G and miglitol had no effect, the phenothiazinium dye thionine acetate was found to be a weak inhibitor. IC<sub>50</sub> values and binding constants for thionine acetate were similar for Slt35 and the hen egg white lysozyme. Molecular docking simulations suggest that thionine binds to the active site of both Slt35 and lysozyme, although it does not make direct interactions with the side-chain of the catalytic Asp and Glu residues as might be expected based on other inhibitors. Thionine acetate also increased the potency of the beta-lactam antibiotic ampicillin against a laboratory strain of <i>E. coli</i>.https://www.mdpi.com/1420-3049/26/14/4189lytic transglycosylasethionine acetateenzyme inhibitionantibacterial
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Aysha B. Mezoughi Chiara M. Costanzo Gregor M. Parker Enas M. Behiry Alan Scott Andrew C. Wood Sarah E. Adams Richard B. Sessions E. Joel Loveridge
spellingShingle	Aysha B. Mezoughi Chiara M. Costanzo Gregor M. Parker Enas M. Behiry Alan Scott Andrew C. Wood Sarah E. Adams Richard B. Sessions E. Joel Loveridge The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i> Molecules lytic transglycosylase thionine acetate enzyme inhibition antibacterial
author_facet	Aysha B. Mezoughi Chiara M. Costanzo Gregor M. Parker Enas M. Behiry Alan Scott Andrew C. Wood Sarah E. Adams Richard B. Sessions E. Joel Loveridge
author_sort	Aysha B. Mezoughi
title	The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_short	The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_full	The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_fullStr	The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_full_unstemmed	The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>
title_sort	lysozyme inhibitor thionine acetate is also an inhibitor of the soluble lytic transglycosylase slt35 from <i>escherichia coli</i>
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2021-07-01
description	Lytic transglycosylases such as Slt35 from <i>E. coli</i> are enzymes involved in bacterial cell wall remodelling and recycling, which represent potential targets for novel antibacterial agents. Here, we investigated a series of known glycosidase inhibitors for their ability to inhibit Slt35. While glycosidase inhibitors such as 1-deoxynojirimycin, castanospermine, thiamet G and miglitol had no effect, the phenothiazinium dye thionine acetate was found to be a weak inhibitor. IC<sub>50</sub> values and binding constants for thionine acetate were similar for Slt35 and the hen egg white lysozyme. Molecular docking simulations suggest that thionine binds to the active site of both Slt35 and lysozyme, although it does not make direct interactions with the side-chain of the catalytic Asp and Glu residues as might be expected based on other inhibitors. Thionine acetate also increased the potency of the beta-lactam antibiotic ampicillin against a laboratory strain of <i>E. coli</i>.
topic	lytic transglycosylase thionine acetate enzyme inhibition antibacterial
url	https://www.mdpi.com/1420-3049/26/14/4189
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The Lysozyme Inhibitor Thionine Acetate Is Also an Inhibitor of the Soluble Lytic Transglycosylase Slt35 from <i>Escherichia coli</i>

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