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The Cytolytic Activity of Vaginolysin Strictly Depends on Cholesterol and Is Potentiated by Human CD59

Gardnerella vaginalis produces cytolysin vaginolysin (VLY), which has been suggested to be a contributor to bacterial vaginosis pathogenesis. VLY along with intermedilysin (ILY) from Streptococcus intermedius have been attributed to a group of cholesterol-dependent cytolysins (CDCs) whose pore-formi...

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Autores principales: Zilnyte, Milda, Venclovas, Česlovas, Zvirbliene, Aurelija, Pleckaityte, Milda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303817/
https://www.ncbi.nlm.nih.gov/pubmed/25590277
http://dx.doi.org/10.3390/toxins7010110
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author Zilnyte, Milda
Venclovas, Česlovas
Zvirbliene, Aurelija
Pleckaityte, Milda
author_facet Zilnyte, Milda
Venclovas, Česlovas
Zvirbliene, Aurelija
Pleckaityte, Milda
author_sort Zilnyte, Milda
collection PubMed
description Gardnerella vaginalis produces cytolysin vaginolysin (VLY), which has been suggested to be a contributor to bacterial vaginosis pathogenesis. VLY along with intermedilysin (ILY) from Streptococcus intermedius have been attributed to a group of cholesterol-dependent cytolysins (CDCs) whose pore-forming activity depends on human CD59 (hCD59). Here, we show that different types of cells lacking hCD59 are susceptible to VLY-mediated lysis, albeit to different extents. We analyze the effects of both hCD59 and cholesterol on VLY cytolytic activity. We show that VLY binds to cholesterol-rich membranes of non-human cells, while VLY with an impaired cholesterol recognition site retains binding to the hCD59-containing cells. We further demonstrate that cholesterol binding by VLY is sufficient to trigger the formation of oligomeric complexes on cholesterol rich-liposomes lacking hCD59. Thus, VLY may induce cell lysis following two alternative pathways. One requires only cholesterol and does not depend on hCD59. The second pathway involves hCD59 contribution similarly to ILY. Apparently, under physiological conditions VLY acts in the most effective way by accepting the assistance of hCD59.
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spelling pubmed-43038172015-02-02 The Cytolytic Activity of Vaginolysin Strictly Depends on Cholesterol and Is Potentiated by Human CD59 Zilnyte, Milda Venclovas, Česlovas Zvirbliene, Aurelija Pleckaityte, Milda Toxins (Basel) Article Gardnerella vaginalis produces cytolysin vaginolysin (VLY), which has been suggested to be a contributor to bacterial vaginosis pathogenesis. VLY along with intermedilysin (ILY) from Streptococcus intermedius have been attributed to a group of cholesterol-dependent cytolysins (CDCs) whose pore-forming activity depends on human CD59 (hCD59). Here, we show that different types of cells lacking hCD59 are susceptible to VLY-mediated lysis, albeit to different extents. We analyze the effects of both hCD59 and cholesterol on VLY cytolytic activity. We show that VLY binds to cholesterol-rich membranes of non-human cells, while VLY with an impaired cholesterol recognition site retains binding to the hCD59-containing cells. We further demonstrate that cholesterol binding by VLY is sufficient to trigger the formation of oligomeric complexes on cholesterol rich-liposomes lacking hCD59. Thus, VLY may induce cell lysis following two alternative pathways. One requires only cholesterol and does not depend on hCD59. The second pathway involves hCD59 contribution similarly to ILY. Apparently, under physiological conditions VLY acts in the most effective way by accepting the assistance of hCD59. MDPI 2015-01-13 /pmc/articles/PMC4303817/ /pubmed/25590277 http://dx.doi.org/10.3390/toxins7010110 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zilnyte, Milda
Venclovas, Česlovas
Zvirbliene, Aurelija
Pleckaityte, Milda
The Cytolytic Activity of Vaginolysin Strictly Depends on Cholesterol and Is Potentiated by Human CD59
title The Cytolytic Activity of Vaginolysin Strictly Depends on Cholesterol and Is Potentiated by Human CD59
title_full The Cytolytic Activity of Vaginolysin Strictly Depends on Cholesterol and Is Potentiated by Human CD59
title_fullStr The Cytolytic Activity of Vaginolysin Strictly Depends on Cholesterol and Is Potentiated by Human CD59
title_full_unstemmed The Cytolytic Activity of Vaginolysin Strictly Depends on Cholesterol and Is Potentiated by Human CD59
title_short The Cytolytic Activity of Vaginolysin Strictly Depends on Cholesterol and Is Potentiated by Human CD59
title_sort cytolytic activity of vaginolysin strictly depends on cholesterol and is potentiated by human cd59
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303817/
https://www.ncbi.nlm.nih.gov/pubmed/25590277
http://dx.doi.org/10.3390/toxins7010110
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