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Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin

Vibrio cholerae cytolysin (VCC) is a β-barrel pore-forming toxin (β-PFT). Upon encountering the target cells, VCC forms heptameric β-barrel pores and permeabilizes the cell membranes. Structure-function mechanisms of VCC have been extensively studied in the past. However, the existence of any natura...

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Autores principales: Singh, Mahendra, Rupesh, N., Pandit, Shashi Bhushan, Chattopadhyay, Kausik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818996/
https://www.ncbi.nlm.nih.gov/pubmed/35140698
http://dx.doi.org/10.3389/fmicb.2021.809782
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author Singh, Mahendra
Rupesh, N.
Pandit, Shashi Bhushan
Chattopadhyay, Kausik
author_facet Singh, Mahendra
Rupesh, N.
Pandit, Shashi Bhushan
Chattopadhyay, Kausik
author_sort Singh, Mahendra
collection PubMed
description Vibrio cholerae cytolysin (VCC) is a β-barrel pore-forming toxin (β-PFT). Upon encountering the target cells, VCC forms heptameric β-barrel pores and permeabilizes the cell membranes. Structure-function mechanisms of VCC have been extensively studied in the past. However, the existence of any natural inhibitor for VCC has not been reported yet. In the present study, we show that curcumin can compromise the membrane-damaging activity of VCC. Curcumin is known to modulate a wide variety of biological processes and functions. However, the application of curcumin in the physiological scenario often gets limited due to its extremely poor solubility in the aqueous environment. Interestingly, we find that VCC can associate with the insoluble fraction of curcumin in the aqueous medium and thus gets separated from the solution phase. This, in turn, reduces the availability of VCC to attack the target membranes and thus blocks the membrane-damaging action of the toxin. We also observe that the soluble aqueous extract of curcumin, generated by the heat treatment, compromises the pore-forming activity of VCC. Interestingly, in the presence of such soluble extract of curcumin, VCC binds to the target membranes and forms the oligomeric assembly. However, such oligomers appear to be non-functional, devoid of the pore-forming activity. The ability of curcumin to bind to VCC and neutralize its membrane-damaging activity suggests that curcumin has the potential to act as an inhibitor of this potent bacterial β-PFT.
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spelling pubmed-88189962022-02-08 Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin Singh, Mahendra Rupesh, N. Pandit, Shashi Bhushan Chattopadhyay, Kausik Front Microbiol Microbiology Vibrio cholerae cytolysin (VCC) is a β-barrel pore-forming toxin (β-PFT). Upon encountering the target cells, VCC forms heptameric β-barrel pores and permeabilizes the cell membranes. Structure-function mechanisms of VCC have been extensively studied in the past. However, the existence of any natural inhibitor for VCC has not been reported yet. In the present study, we show that curcumin can compromise the membrane-damaging activity of VCC. Curcumin is known to modulate a wide variety of biological processes and functions. However, the application of curcumin in the physiological scenario often gets limited due to its extremely poor solubility in the aqueous environment. Interestingly, we find that VCC can associate with the insoluble fraction of curcumin in the aqueous medium and thus gets separated from the solution phase. This, in turn, reduces the availability of VCC to attack the target membranes and thus blocks the membrane-damaging action of the toxin. We also observe that the soluble aqueous extract of curcumin, generated by the heat treatment, compromises the pore-forming activity of VCC. Interestingly, in the presence of such soluble extract of curcumin, VCC binds to the target membranes and forms the oligomeric assembly. However, such oligomers appear to be non-functional, devoid of the pore-forming activity. The ability of curcumin to bind to VCC and neutralize its membrane-damaging activity suggests that curcumin has the potential to act as an inhibitor of this potent bacterial β-PFT. Frontiers Media S.A. 2022-01-24 /pmc/articles/PMC8818996/ /pubmed/35140698 http://dx.doi.org/10.3389/fmicb.2021.809782 Text en Copyright © 2022 Singh, Rupesh, Pandit and Chattopadhyay. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Singh, Mahendra
Rupesh, N.
Pandit, Shashi Bhushan
Chattopadhyay, Kausik
Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin
title Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin
title_full Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin
title_fullStr Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin
title_full_unstemmed Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin
title_short Curcumin Inhibits Membrane-Damaging Pore-Forming Function of the β-Barrel Pore-Forming Toxin Vibrio cholerae Cytolysin
title_sort curcumin inhibits membrane-damaging pore-forming function of the β-barrel pore-forming toxin vibrio cholerae cytolysin
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818996/
https://www.ncbi.nlm.nih.gov/pubmed/35140698
http://dx.doi.org/10.3389/fmicb.2021.809782
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