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- Title
Regulation of CovR expression in Group B Streptococcus impacts blood–brain barrier penetration.
- Authors
Lembo, Annalisa; Gurney, Michael A.; Burnside, Kellie; Banerjee, Anirban; Reyes, Melissa de los; Connelly, James E.; Wan-Jung Lin; Jewell, Kelsea A.; Vo, Anthony; Renken, Christian W.; Doran, Kelly S.; Rajagopal, Lakshmi
- 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 β-haemolysin/cytolysin (β-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 β-H/C and other virulence factors in response to the environment. GBS can repress transcription of β-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 β-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
STREPTOCOCCUS; BLOOD-brain barrier; INFECTION; PATHOGENIC microorganisms; BACTERIOLOGY; MOLECULAR microbiology
- Publication
Molecular Microbiology, 2010, Vol 77, Issue 2, p431
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/j.1365-2958.2010.07215.x