Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro.

<h4>Background</h4>Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of life-threatening neonatal meningitis and survivors often suffer permanent neurological damage. How this organism interacts with the meninges and subsequently with astrocytes that constitute the...

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Autores principales:	Khalil Alkuwaity, Alexander Taylor, John E Heckels, Kelly S Doran, Myron Christodoulides
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/95c188053ceb455b9bddbb77426e0dc5
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spelling	oai:doaj.org-article:95c188053ceb455b9bddbb77426e0dc52021-11-18T07:09:07ZGroup B Streptococcus interactions with human meningeal cells and astrocytes in vitro.1932-620310.1371/journal.pone.0042660https://doaj.org/article/95c188053ceb455b9bddbb77426e0dc52012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22900037/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of life-threatening neonatal meningitis and survivors often suffer permanent neurological damage. How this organism interacts with the meninges and subsequently with astrocytes that constitute the underlying cortical glia limitans superficialis is not known.<h4>Methodology/principal findings</h4>In this paper, we demonstrate dose-dependent adherence of GBS over time to human meningioma cells and fetal astrocytes in vitro, which was not influenced by expression of either β-haemolysin/cytolysin (β-h/c) toxin, different capsule serotypes or by absence of capsule (p>0.05). Internalization of GBS by both cell types was, however, a slow and an infrequent event (only 0.02-0.4% of associated bacteria were internalised by 9 h). Expression of β-h/c toxin did not play a role in invasion (p>0.05), whereas capsule expression lead to a reduction (p<0.05) in the numbers of intracellular bacteria recovered. GBS strains induced cytotoxicity as demonstrated by the measurement of lactate dehydrogenase (LDH) enzyme release by 9 h and by viable staining. Increasing levels of meningioma cell death correlated with bacterial growth and the phenotype of β-h/c toxin production, i.e. from weakly, to normo- to hyper-haemolytic. However, cytotoxicity was significantly greater (p<0.05) towards astrocytes, and infection with initial MOI≥0.003 induced 70-100% LDH release. By comparing wild-type (β-h/c(+)) and mutant (ΔcylE β-h/c(-)) strains and β-h/c toxin extracts and by using the surfactant dipalmitoylphosphatidylcholine in cytotoxicity inhibition experiments, β-h/c toxin was demonstrated as principally responsible for cell death.<h4>Conclusions/significance</h4>This study has described key events in the interactions of GBS with meningeal cells and astrocytes in vitro and a major virulence role for β-h/c toxin. Understanding the mechanisms involved will help to identify potential therapies for improving patient survival and for reducing the incidence and severity of neurological sequelae.Khalil AlkuwaityAlexander TaylorJohn E HeckelsKelly S DoranMyron ChristodoulidesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42660 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Khalil Alkuwaity Alexander Taylor John E Heckels Kelly S Doran Myron Christodoulides Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro.
description	<h4>Background</h4>Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of life-threatening neonatal meningitis and survivors often suffer permanent neurological damage. How this organism interacts with the meninges and subsequently with astrocytes that constitute the underlying cortical glia limitans superficialis is not known.<h4>Methodology/principal findings</h4>In this paper, we demonstrate dose-dependent adherence of GBS over time to human meningioma cells and fetal astrocytes in vitro, which was not influenced by expression of either β-haemolysin/cytolysin (β-h/c) toxin, different capsule serotypes or by absence of capsule (p>0.05). Internalization of GBS by both cell types was, however, a slow and an infrequent event (only 0.02-0.4% of associated bacteria were internalised by 9 h). Expression of β-h/c toxin did not play a role in invasion (p>0.05), whereas capsule expression lead to a reduction (p<0.05) in the numbers of intracellular bacteria recovered. GBS strains induced cytotoxicity as demonstrated by the measurement of lactate dehydrogenase (LDH) enzyme release by 9 h and by viable staining. Increasing levels of meningioma cell death correlated with bacterial growth and the phenotype of β-h/c toxin production, i.e. from weakly, to normo- to hyper-haemolytic. However, cytotoxicity was significantly greater (p<0.05) towards astrocytes, and infection with initial MOI≥0.003 induced 70-100% LDH release. By comparing wild-type (β-h/c(+)) and mutant (ΔcylE β-h/c(-)) strains and β-h/c toxin extracts and by using the surfactant dipalmitoylphosphatidylcholine in cytotoxicity inhibition experiments, β-h/c toxin was demonstrated as principally responsible for cell death.<h4>Conclusions/significance</h4>This study has described key events in the interactions of GBS with meningeal cells and astrocytes in vitro and a major virulence role for β-h/c toxin. Understanding the mechanisms involved will help to identify potential therapies for improving patient survival and for reducing the incidence and severity of neurological sequelae.
format	article
author	Khalil Alkuwaity Alexander Taylor John E Heckels Kelly S Doran Myron Christodoulides
author_facet	Khalil Alkuwaity Alexander Taylor John E Heckels Kelly S Doran Myron Christodoulides
author_sort	Khalil Alkuwaity
title	Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro.
title_short	Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro.
title_full	Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro.
title_fullStr	Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro.
title_full_unstemmed	Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro.
title_sort	group b streptococcus interactions with human meningeal cells and astrocytes in vitro.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/95c188053ceb455b9bddbb77426e0dc5
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_version_	1718423867902394368

Group B Streptococcus interactions with human meningeal cells and astrocytes in vitro.

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