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CpsR, a GntR family regulator, transcriptionally regulates capsular polysaccharide biosynthesis and governs bacterial virulence in Streptococcus pneumoniae.
- Source :
-
Scientific reports [Sci Rep] 2016 Jul 08; Vol. 6, pp. 29255. Date of Electronic Publication: 2016 Jul 08. - Publication Year :
- 2016
-
Abstract
- Transcriptional regulation of capsule expression is critical for pneumococcal transition from carriage to infection, yet the underlying mechanism remains incompletely understood. Here, we describe the regulation of capsular polysaccharide, one of the most important pneumococcal virulence factor by a GntR family regulator, CpsR. Electrophoretic mobility-shift assays have shown the direct interaction between CpsR and the cps promoter (cpsp), and their interaction could be competitively interfered by glucose. DNase I footprinting assays localized the binding site to a region -146 to -114 base pairs relative to the transcriptional start site of the cps locus in S. pneumoniae D39. We found that CpsR negatively controlled the transcription of the cps locus and hence CPS production, which was confirmed by fine-tuning expression of CpsR in a ΔcpsR complemented strain. Increased expression of CpsR in complemented strain led to a decreased resistance to the whole-blood-mediated killing, suggesting a protective role for CpsR-cpsp interaction in the establishment of invasive infection. Finally, animal experiments showed that CpsR-cpsp interaction was necessary for both pneumococcal colonization and invasive infection. Taken together, our results provide a thorough insight into the regulation of capsule production mediated by CpsR and its important roles in pneumococcal pathogenesis.
- Subjects :
- Animals
Bacterial Proteins genetics
Binding Sites
Blood Bactericidal Activity
DNA Footprinting
DNA, Bacterial metabolism
Electrophoretic Mobility Shift Assay
Gene Deletion
Genetic Complementation Test
Mice, Inbred BALB C
Pneumococcal Infections microbiology
Pneumococcal Infections pathology
Promoter Regions, Genetic
Protein Binding
Streptococcus pneumoniae genetics
Survival Analysis
Transcription Factors genetics
Transcription, Genetic
Virulence
Bacterial Proteins metabolism
Gene Expression Regulation, Bacterial
Polysaccharides, Bacterial biosynthesis
Streptococcus pneumoniae metabolism
Streptococcus pneumoniae pathogenicity
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27386955
- Full Text :
- https://doi.org/10.1038/srep29255