دورية أكاديمية
Group B Streptococcus transcriptome when interacting with brain endothelial cells.
| العنوان: | Group B Streptococcus transcriptome when interacting with brain endothelial cells. |
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| المؤلفون: | Vollmuth N; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA., Bridgers BE; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA., Armstrong ML; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA., Wood JF; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA., Gildea AR; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA., Espinal ER; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA., Hooven TA; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Richard King Mellon Institute for Pediatric Research, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA., Barbieri G; Department of Biology and Biotechnology, University of Pavia, Pavia, Italy., Westermann AJ; Institute of Molecular Infection Biology (IMIB), University of Wuerzburg, Wuerzburg, Germany.; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), Wuerzburg, Germany., Sauerwein T; Institute of Molecular Infection Biology (IMIB), University of Wuerzburg, Wuerzburg, Germany.; ZB MED, Information Centre for Life Sciences, Cologne, Germany., Foerstner KU; Institute of Molecular Infection Biology (IMIB), University of Wuerzburg, Wuerzburg, Germany.; ZB MED, Information Centre for Life Sciences, Cologne, Germany.; TH Koeln, University of Applied Sciences, Cologne, Germany., Schubert-Unkmeir A; Institute for Hygiene and Microbiology, University of Wuerzburg, Wuerzburg, Germany., Kim BJ; Department of Biological Sciences, University of Alabama, Tuscaloosa, Alabama, USA.; Department of Microbiology, University of Alabama at Birmingham Heesink School of Medicine, Birmingham, Alabama, USA.; University of Alabama Center of Convergent Biosciences and Medicine, Tuscaloosa, Alabama, USA.; University of Alabama Life Research, Tuscaloosa, Alabama, USA. |
| المصدر: | Journal of bacteriology [J Bacteriol] 2024 Jun 20; Vol. 206 (6), pp. e0008724. Date of Electronic Publication: 2024 May 21. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 2985120R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5530 (Electronic) Linking ISSN: 00219193 NLM ISO Abbreviation: J Bacteriol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Society for Microbiology |
| مواضيع طبية MeSH: | Streptococcus agalactiae*/genetics , Streptococcus agalactiae*/metabolism , Streptococcus agalactiae*/pathogenicity , Endothelial Cells*/microbiology , Transcriptome* , Brain*/microbiology , Brain*/metabolism, Humans ; Blood-Brain Barrier/microbiology ; Blood-Brain Barrier/metabolism ; Gene Expression Regulation, Bacterial ; Virulence Factors/genetics ; Virulence Factors/metabolism ; Virulence ; Streptococcal Infections/microbiology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Meningitis, Bacterial/microbiology |
| مستخلص: | Bacterial meningitis is a life-threatening infection of the central nervous system (CNS) that occurs when bacteria are able to cross the blood-brain barrier (BBB) or the meningeal-cerebrospinal fluid barrier (mBCSFB). The BBB and mBCSFB comprise highly specialized brain endothelial cells (BECs) that typically restrict pathogen entry. Group B Streptococcus (GBS or Streptococcus agalactiae ) is the leading cause of neonatal meningitis. Until recently, identification of GBS virulence factors has relied on genetic screening approaches. Instead, we here conducted RNA-seq analysis on GBS when interacting with induced pluripotent stem cell-derived BECs (iBECs) to pinpoint virulence-associated genes. Of the 2,068 annotated protein-coding genes of GBS, 430 transcripts displayed significant changes in expression after interacting with BECs. Notably, we found that the majority of differentially expressed GBS transcripts were downregulated (360 genes) during infection of iBECs. Interestingly, codY , encoding a pleiotropic transcriptional repressor in low-G + C Gram-positive bacteria, was identified as being highly downregulated. We conducted qPCR to confirm the codY downregulation observed via RNA-seq during the GBS-iBEC interaction and obtained codY mutants in three different GBS background parental strains. As anticipated from the RNA-seq results, the [Formula: see text] codY strains were more adherent and invasive in two in vitro BEC models. Together, this demonstrates the utility of RNA-seq during the BEC interaction to identify GBS virulence modulators. Importance: Group B Streptococcus (GBS) meningitis remains the leading cause of neonatal meningitis. Research work has identified surface factors and two-component systems that contribute to GBS disruption of the blood-brain barrier (BBB). These discoveries often relied on genetic screening approaches. Here, we provide transcriptomic data describing how GBS changes its transcriptome when interacting with brain endothelial cells. Additionally, we have phenotypically validated these data by obtaining mutants of a select regulator that is highly down-regulated during infection and testing on our BBB model. This work provides the research field with a validated data set that can provide an insight into potential pathways that GBS requires to interact with the BBB and open the door to new discoveries. Competing Interests: The authors declare no conflict of interest. |
| معلومات مُعتمدة: | Alexander von Humboldt-Stiftung (AvH); R15NS131921 HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS); R21 AI147511 United States AI NIAID NIH HHS; K08 AI132555 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: Group B Streptococcus; Streptococcus agalactiae; blood–brain barrier; brain endothelial cells; transcriptome |
| المشرفين على المادة: | 0 (Virulence Factors) 0 (Bacterial Proteins) |
| تواريخ الأحداث: | Date Created: 20240521 Date Completed: 20240620 Latest Revision: 20240808 |
| رمز التحديث: | 20240808 |
| DOI: | 10.1128/jb.00087-24 |
| PMID: | 38771039 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5530 |
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| DOI: | 10.1128/jb.00087-24 |