Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells
| Autor: | Kelly S. Doran, Andrew S. Cutting, Thomas A. Weston, Lara Stewart, Nicholas Villarino, Yvette Del Rosario, Rong Mu, Kathryn A. Patras |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Mutant lcsh:Medicine Fluorescent Antibody Technique Gene Expression medicine.disease_cause Pathology and Laboratory Medicine Bacterial Adhesion Epithelium Mice 0302 clinical medicine Cell Movement Animal Cells Genes Regulator Medicine and Health Sciences lcsh:Science Cells Cultured Multidisciplinary Virulence Microbial Genetics Brain 3. Good health Bacterial Pathogens Mutant Strains medicine.anatomical_structure Intracellular Pathogens Blood-Brain Barrier Medical Microbiology Cellular Structures and Organelles Pathogens Cellular Types Anatomy Intracellular Research Article 030106 microbiology Biology Blood–brain barrier Microbiology Bacterial genetics Neonatal meningitis Streptococcus agalactiae 03 medical and health sciences Bacterial Proteins 030225 pediatrics Streptococcal Infections medicine Genetics Animals Humans Bacterial Genetics Gene Regulation Vesicles Microbial Pathogens Intracellular parasite lcsh:R Biology and Life Sciences Endothelial Cells Biological Transport Epithelial Cells Bacteriology Gene Expression Regulation Bacterial Cell Biology medicine.disease Immunity Innate Biological Tissue Mutation lcsh:Q Endothelium Vascular Lysosomes Protein Kinases |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 4, p e0153891 (2016) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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