Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>

ABSTRACT Group B Streptococcus (GBS) remains the leading cause of neonatal meningitis, a disease associated with high rates of adverse neurological sequelae. The in vivo relationship between GBS and brain tissues remains poorly characterized, partly because past studies had focused on microbial rath...

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Autores principales:	Anaamika Campeau, Robert H. Mills, Marie Blanchette, Kaja Bajc, Mario Malfavon, Roeben N. Munji, Liwen Deng, Bryan Hancock, Kathryn A. Patras, Joshua Olson, Victor Nizet, Richard Daneman, Kelly Doran, David J. Gonzalez
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	group B Streptococcus TMT blood-brain barrier meningitis multiplexing proteomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6937f2e3052a4afdbe7d31c35a75fdc5
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spelling	oai:doaj.org-article:6937f2e3052a4afdbe7d31c35a75fdc52021-12-02T19:47:35ZMultidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>10.1128/mSystems.00368-202379-5077https://doaj.org/article/6937f2e3052a4afdbe7d31c35a75fdc52020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00368-20https://doaj.org/toc/2379-5077ABSTRACT Group B Streptococcus (GBS) remains the leading cause of neonatal meningitis, a disease associated with high rates of adverse neurological sequelae. The in vivo relationship between GBS and brain tissues remains poorly characterized, partly because past studies had focused on microbial rather than host processes. Additionally, the field has not capitalized on systems-level technologies to probe the host-pathogen relationship. Here, we use multiplexed quantitative proteomics to investigate the effect of GBS infection in the murine brain at various levels of tissue complexity, beginning with the whole organ and moving to brain vascular substructures. Infected whole brains showed classical signatures associated with the acute-phase response. In isolated brain microvessels, classical blood-brain barrier proteins were unaltered, but interferon signaling and leukocyte recruitment proteins were upregulated. The choroid plexus showed increases in peripheral immune cell proteins. Proteins that increased in abundance in the vasculature during GBS invasion were associated with major histocompatibility complex (MHC) class I antigen processing and endoplasmic reticulum dysfunction, a finding which correlated with altered host protein glycosylation profiles. Globally, there was low concordance between the infection proteome of whole brains and isolated vascular tissues. This report underscores the utility of unbiased, systems-scale analyses of functional tissue substructures for understanding disease. IMPORTANCE Group B Streptococcus (GBS) meningitis remains a major cause of poor health outcomes very early in life. Both the host-pathogen relationship leading to disease and the massive host response to infection contributing to these poor outcomes are orchestrated at the tissue and cell type levels. GBS meningitis is thought to result when bacteria present in the blood circumvent the selectively permeable vascular barriers that feed the brain. Additionally, tissue damage subsequent to bacterial invasion is mediated by inflammation and by immune cells from the periphery crossing the blood-brain barrier. Indeed, the vasculature plays a central role in disease processes occurring during GBS infection of the brain. Here, we employed quantitative proteomic analysis of brain vascular substructures during invasive GBS disease. We used the generated data to map molecular alterations associated with tissue perturbation, finding widespread intracellular dysfunction and punctuating the importance of investigations relegated to tissue type over the whole organ.Anaamika CampeauRobert H. MillsMarie BlanchetteKaja BajcMario MalfavonRoeben N. MunjiLiwen DengBryan HancockKathryn A. PatrasJoshua OlsonVictor NizetRichard DanemanKelly DoranDavid J. GonzalezAmerican Society for Microbiologyarticlegroup B StreptococcusTMTblood-brain barriermeningitismultiplexingproteomicsMicrobiologyQR1-502ENmSystems, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	group B Streptococcus TMT blood-brain barrier meningitis multiplexing proteomics Microbiology QR1-502
spellingShingle	group B Streptococcus TMT blood-brain barrier meningitis multiplexing proteomics Microbiology QR1-502 Anaamika Campeau Robert H. Mills Marie Blanchette Kaja Bajc Mario Malfavon Roeben N. Munji Liwen Deng Bryan Hancock Kathryn A. Patras Joshua Olson Victor Nizet Richard Daneman Kelly Doran David J. Gonzalez Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>
description	ABSTRACT Group B Streptococcus (GBS) remains the leading cause of neonatal meningitis, a disease associated with high rates of adverse neurological sequelae. The in vivo relationship between GBS and brain tissues remains poorly characterized, partly because past studies had focused on microbial rather than host processes. Additionally, the field has not capitalized on systems-level technologies to probe the host-pathogen relationship. Here, we use multiplexed quantitative proteomics to investigate the effect of GBS infection in the murine brain at various levels of tissue complexity, beginning with the whole organ and moving to brain vascular substructures. Infected whole brains showed classical signatures associated with the acute-phase response. In isolated brain microvessels, classical blood-brain barrier proteins were unaltered, but interferon signaling and leukocyte recruitment proteins were upregulated. The choroid plexus showed increases in peripheral immune cell proteins. Proteins that increased in abundance in the vasculature during GBS invasion were associated with major histocompatibility complex (MHC) class I antigen processing and endoplasmic reticulum dysfunction, a finding which correlated with altered host protein glycosylation profiles. Globally, there was low concordance between the infection proteome of whole brains and isolated vascular tissues. This report underscores the utility of unbiased, systems-scale analyses of functional tissue substructures for understanding disease. IMPORTANCE Group B Streptococcus (GBS) meningitis remains a major cause of poor health outcomes very early in life. Both the host-pathogen relationship leading to disease and the massive host response to infection contributing to these poor outcomes are orchestrated at the tissue and cell type levels. GBS meningitis is thought to result when bacteria present in the blood circumvent the selectively permeable vascular barriers that feed the brain. Additionally, tissue damage subsequent to bacterial invasion is mediated by inflammation and by immune cells from the periphery crossing the blood-brain barrier. Indeed, the vasculature plays a central role in disease processes occurring during GBS infection of the brain. Here, we employed quantitative proteomic analysis of brain vascular substructures during invasive GBS disease. We used the generated data to map molecular alterations associated with tissue perturbation, finding widespread intracellular dysfunction and punctuating the importance of investigations relegated to tissue type over the whole organ.
format	article
author	Anaamika Campeau Robert H. Mills Marie Blanchette Kaja Bajc Mario Malfavon Roeben N. Munji Liwen Deng Bryan Hancock Kathryn A. Patras Joshua Olson Victor Nizet Richard Daneman Kelly Doran David J. Gonzalez
author_facet	Anaamika Campeau Robert H. Mills Marie Blanchette Kaja Bajc Mario Malfavon Roeben N. Munji Liwen Deng Bryan Hancock Kathryn A. Patras Joshua Olson Victor Nizet Richard Daneman Kelly Doran David J. Gonzalez
author_sort	Anaamika Campeau
title	Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>
title_short	Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>
title_full	Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>
title_fullStr	Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>
title_full_unstemmed	Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>
title_sort	multidimensional proteome profiling of blood-brain barrier perturbation by group b <italic toggle="yes">streptococcus</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/6937f2e3052a4afdbe7d31c35a75fdc5
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Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B <italic toggle="yes">Streptococcus</italic>

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