Environmental pH modulates inerolysin activity via post-binding blockade

Abstract The cholesterol dependent cytolysins (CDCs) are a family of pore-forming toxins produced by a wide range of bacteria. Some CDCs are important virulence factors for their cognate organisms, but their activity must be tightly regulated to ensure they operate at appropriate times and within th...

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Autores principales:	Ryan Rampersaud, Emma L. Lewis, Timothy J. LaRocca, Adam J. Ratner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aea011bfef974b26a9bb104e9cc10ed8
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spelling	oai:doaj.org-article:aea011bfef974b26a9bb104e9cc10ed82021-12-02T15:07:44ZEnvironmental pH modulates inerolysin activity via post-binding blockade10.1038/s41598-018-19994-82045-2322https://doaj.org/article/aea011bfef974b26a9bb104e9cc10ed82018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19994-8https://doaj.org/toc/2045-2322Abstract The cholesterol dependent cytolysins (CDCs) are a family of pore-forming toxins produced by a wide range of bacteria. Some CDCs are important virulence factors for their cognate organisms, but their activity must be tightly regulated to ensure they operate at appropriate times and within the appropriate subcellular compartments. pH-dependent activity has been described for several CDCs, but the mechanism of such regulation has been studied in depth only for listeriolysin O (LLO), which senses environmental pH through a triad of acidic residues that mediate protein unfolding. Here we present data supporting a distinct mechanism for pH-dependence for inerolysin (INY), the CDC produced by Lactobacillus iners. Inerolysin (INY) has an acidic pH optimum with loss of activity at neutral pH. INY pH-dependence is characterized by reversible loss of pore formation with preservation of membrane binding. Fluorescent membrane probe assays indicated that INY insertion into host cell membranes, but not oligomerization, was defective at neutral pH. These data support the existence of a newly appreciated form of CDC pH-dependence functioning at a late stage of pore formation.Ryan RampersaudEmma L. LewisTimothy J. LaRoccaAdam J. RatnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryan Rampersaud Emma L. Lewis Timothy J. LaRocca Adam J. Ratner Environmental pH modulates inerolysin activity via post-binding blockade
description	Abstract The cholesterol dependent cytolysins (CDCs) are a family of pore-forming toxins produced by a wide range of bacteria. Some CDCs are important virulence factors for their cognate organisms, but their activity must be tightly regulated to ensure they operate at appropriate times and within the appropriate subcellular compartments. pH-dependent activity has been described for several CDCs, but the mechanism of such regulation has been studied in depth only for listeriolysin O (LLO), which senses environmental pH through a triad of acidic residues that mediate protein unfolding. Here we present data supporting a distinct mechanism for pH-dependence for inerolysin (INY), the CDC produced by Lactobacillus iners. Inerolysin (INY) has an acidic pH optimum with loss of activity at neutral pH. INY pH-dependence is characterized by reversible loss of pore formation with preservation of membrane binding. Fluorescent membrane probe assays indicated that INY insertion into host cell membranes, but not oligomerization, was defective at neutral pH. These data support the existence of a newly appreciated form of CDC pH-dependence functioning at a late stage of pore formation.
format	article
author	Ryan Rampersaud Emma L. Lewis Timothy J. LaRocca Adam J. Ratner
author_facet	Ryan Rampersaud Emma L. Lewis Timothy J. LaRocca Adam J. Ratner
author_sort	Ryan Rampersaud
title	Environmental pH modulates inerolysin activity via post-binding blockade
title_short	Environmental pH modulates inerolysin activity via post-binding blockade
title_full	Environmental pH modulates inerolysin activity via post-binding blockade
title_fullStr	Environmental pH modulates inerolysin activity via post-binding blockade
title_full_unstemmed	Environmental pH modulates inerolysin activity via post-binding blockade
title_sort	environmental ph modulates inerolysin activity via post-binding blockade
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/aea011bfef974b26a9bb104e9cc10ed8
work_keys_str_mv	AT ryanrampersaud environmentalphmodulatesinerolysinactivityviapostbindingblockade AT emmallewis environmentalphmodulatesinerolysinactivityviapostbindingblockade AT timothyjlarocca environmentalphmodulatesinerolysinactivityviapostbindingblockade AT adamjratner environmentalphmodulatesinerolysinactivityviapostbindingblockade
_version_	1718388410087899136

Environmental pH modulates inerolysin activity via post-binding blockade

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