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Regulation of CovR expression in Group B Streptococcus impacts blood-brain barrier penetration.
- Source :
-
Molecular microbiology [Mol Microbiol] 2010 Jul; Vol. 77 (2), pp. 431-43. Date of Electronic Publication: 2010 May 19. - Publication Year :
- 2010
-
Abstract
- Group B Streptococcus (GBS) is an important cause of invasive infections in humans. The pathogen encodes a number of virulence factors including the pluripotent beta-haemolysin/cytolysin (beta-H/C). As GBS has the disposition of both a commensal organism and an invasive pathogen, it is important for the organism to appropriately regulate beta-H/C and other virulence factors in response to the environment. GBS can repress transcription of beta-H/C using the two-component system, CovR/CovS. Recently, we described that the serine/threonine kinase Stk1 can phosphorylate CovR at threonine 65 to relieve repression of beta-H/C. In this study, we show that infection with CovR-deficient GBS strains resulted in increased sepsis. Although CovR-deficient GBS showed decreased ability to invade the brain endothelium in vitro, they were more proficient in induction of permeability and pro-inflammatory signalling pathways in brain endothelium and penetration of the blood-brain barrier (BBB) in vivo. Microarray analysis revealed that CovR positively regulates its own expression and regulates the expression of 153 genes. Collectively, our results suggest that the positive feedback loop which regulates CovR transcription modulates host cell interaction and immune defence and may facilitate the transition of GBS from a commensal organism to a virulent meningeal pathogen.
- Subjects :
- Animals
Bacterial Proteins genetics
Cell Line
Gene Expression Regulation, Bacterial
Humans
Male
Mice
Oligonucleotide Array Sequence Analysis
Protein Processing, Post-Translational
RNA, Bacterial genetics
Repressor Proteins genetics
Sepsis microbiology
Streptococcus agalactiae genetics
Streptococcus agalactiae pathogenicity
Virulence Factors genetics
Virulence Factors metabolism
Bacterial Proteins metabolism
Blood-Brain Barrier microbiology
Repressor Proteins metabolism
Streptococcal Infections microbiology
Streptococcus agalactiae metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2958
- Volume :
- 77
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 20497331
- Full Text :
- https://doi.org/10.1111/j.1365-2958.2010.07215.x