Cargando…
Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells
Group B Streptococcus (GBS) is a major causative agent of neonatal meningitis due to its ability to efficiently cross the blood-brain barrier (BBB) and enter the central nervous system (CNS). It has been demonstrated that GBS can invade human brain microvascular endothelial cells (hBMEC), a primary...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839699/ https://www.ncbi.nlm.nih.gov/pubmed/27100296 http://dx.doi.org/10.1371/journal.pone.0153891 |
_version_ | 1782428167665876992 |
---|---|
author | Mu, Rong Cutting, Andrew S. Del Rosario, Yvette Villarino, Nicholas Stewart, Lara Weston, Thomas A. Patras, Kathryn A. Doran, Kelly S. |
author_facet | Mu, Rong Cutting, Andrew S. Del Rosario, Yvette Villarino, Nicholas Stewart, Lara Weston, Thomas A. Patras, Kathryn A. Doran, Kelly S. |
author_sort | Mu, Rong |
collection | PubMed |
description | Group B Streptococcus (GBS) is a major causative agent of neonatal meningitis due to its ability to efficiently cross the blood-brain barrier (BBB) and enter the central nervous system (CNS). It has been demonstrated that GBS can invade human brain microvascular endothelial cells (hBMEC), a primary component of the BBB; however, the mechanism of intracellular survival and trafficking is unclear. We previously identified a two component regulatory system, CiaR/H, which promotes GBS intracellular survival in hBMEC. Here we show that a GBS strain deficient in the response regulator, CiaR, localized more frequently with Rab5, Rab7 and LAMP1 positive vesicles. Further, lysosomes isolated from hBMEC contained fewer viable bacteria following initial infection with the ΔciaR mutant compared to the WT strain. To characterize the contribution of CiaR-regulated genes, we constructed isogenic mutant strains lacking the two most down-regulated genes in the CiaR-deficient mutant, SAN_2180 and SAN_0039. These genes contributed to bacterial uptake and intracellular survival. Furthermore, competition experiments in mice showed that WT GBS had a significant survival advantage over the Δ2180 and Δ0039 mutants in the bloodstream and brain. |
format | Online Article Text |
id | pubmed-4839699 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48396992016-04-29 Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells Mu, Rong Cutting, Andrew S. Del Rosario, Yvette Villarino, Nicholas Stewart, Lara Weston, Thomas A. Patras, Kathryn A. Doran, Kelly S. PLoS One Research Article Group B Streptococcus (GBS) is a major causative agent of neonatal meningitis due to its ability to efficiently cross the blood-brain barrier (BBB) and enter the central nervous system (CNS). It has been demonstrated that GBS can invade human brain microvascular endothelial cells (hBMEC), a primary component of the BBB; however, the mechanism of intracellular survival and trafficking is unclear. We previously identified a two component regulatory system, CiaR/H, which promotes GBS intracellular survival in hBMEC. Here we show that a GBS strain deficient in the response regulator, CiaR, localized more frequently with Rab5, Rab7 and LAMP1 positive vesicles. Further, lysosomes isolated from hBMEC contained fewer viable bacteria following initial infection with the ΔciaR mutant compared to the WT strain. To characterize the contribution of CiaR-regulated genes, we constructed isogenic mutant strains lacking the two most down-regulated genes in the CiaR-deficient mutant, SAN_2180 and SAN_0039. These genes contributed to bacterial uptake and intracellular survival. Furthermore, competition experiments in mice showed that WT GBS had a significant survival advantage over the Δ2180 and Δ0039 mutants in the bloodstream and brain. Public Library of Science 2016-04-21 /pmc/articles/PMC4839699/ /pubmed/27100296 http://dx.doi.org/10.1371/journal.pone.0153891 Text en © 2016 Mu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Mu, Rong Cutting, Andrew S. Del Rosario, Yvette Villarino, Nicholas Stewart, Lara Weston, Thomas A. Patras, Kathryn A. Doran, Kelly S. Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells |
title | Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells |
title_full | Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells |
title_fullStr | Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells |
title_full_unstemmed | Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells |
title_short | Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells |
title_sort | identification of ciar regulated genes that promote group b streptococcal virulence and interaction with brain endothelial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839699/ https://www.ncbi.nlm.nih.gov/pubmed/27100296 http://dx.doi.org/10.1371/journal.pone.0153891 |
work_keys_str_mv | AT murong identificationofciarregulatedgenesthatpromotegroupbstreptococcalvirulenceandinteractionwithbrainendothelialcells AT cuttingandrews identificationofciarregulatedgenesthatpromotegroupbstreptococcalvirulenceandinteractionwithbrainendothelialcells AT delrosarioyvette identificationofciarregulatedgenesthatpromotegroupbstreptococcalvirulenceandinteractionwithbrainendothelialcells AT villarinonicholas identificationofciarregulatedgenesthatpromotegroupbstreptococcalvirulenceandinteractionwithbrainendothelialcells AT stewartlara identificationofciarregulatedgenesthatpromotegroupbstreptococcalvirulenceandinteractionwithbrainendothelialcells AT westonthomasa identificationofciarregulatedgenesthatpromotegroupbstreptococcalvirulenceandinteractionwithbrainendothelialcells AT patraskathryna identificationofciarregulatedgenesthatpromotegroupbstreptococcalvirulenceandinteractionwithbrainendothelialcells AT dorankellys identificationofciarregulatedgenesthatpromotegroupbstreptococcalvirulenceandinteractionwithbrainendothelialcells |