ArticleVirulence2018
Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis.
Article in Virulence, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- A synopsis of competence-regulated virulence inVirulence · 2026Review
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- Monounsaturated fatty acid biosynthesis is critical for streptococcal envelope homeostasis and stress tolerance.bioRxiv : the preprint server for biology · 2026Article
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- Increased Proportions of Invasive Pneumococcal Disease Cases Among Adults Experiencing Homelessness Sets the Stage for New Serotype 4 Capsular-Switch Recombinants.The Journal of infectious diseases · 2025Article
- Biosynthesis of mitis group streptococcal glycolipids and their roles in physiology and antibiotic susceptibility.bioRxiv : the preprint server for biology · 2024Article
- Contribution of Streptococcus pyogenes M87 protein to innate immune resistance and virulence.Microbial pathogenesis · 2022Article
- Pneumococcal BgaA Promotes Host Organ Bleeding and Coagulation in a Mouse Sepsis Model.Frontiers in cellular and infection microbiology · 2022Article
- Transcriptomic analysis of human brain microvascular endothelial cells exposed to laminin binding protein (adhesion lipoprotein) and Streptococcus pneumoniae.Scientific reports · 2021Article
- Pneumococcal Encounter With the Blood-Brain Barrier Endothelium.Frontiers in cellular and infection microbiology · 2020Review
- Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis.Frontiers in microbiology · 2020Article
- Streptococcal H2O2 inhibits IgE-triggered degranulation of RBL-2H3 mast cell/basophil cell line by inducing cell death.PloS one · 2020Article
- Identification of evolutionarily conserved virulence factor by selective pressure analysis ofCommunications biology · 2019Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Streptococcus pneumoniae is a major pathogen that causes pneumonia, sepsis, and meningitis. The candidate combox site 4 (ccs4) gene has been reported to be a pneumococcal competence-induced gene. Such genes are involved in development of S. pneumoniae competence and virulence, though the functions of ccs4 remain unknown. In the present study, the role of Ccs4 in the pathogenesis of pneumococcal meningitis was examined. We initially constructed a ccs4 deletion mutant and complement strains, then examined their association with and invasion into human brain microvascular endothelial cells. Wild-type and Ccs4-complemented strains exhibited significantly higher rates of association and invasion as compared to the ccs4 mutant strain. Deletion of ccs4 did not change bacterial growth activity or expression of NanA and CbpA, known brain endothelial pneumococcal adhesins. Next, mice were infected either intravenously or intranasally with pneumococcal strains. In the intranasal infection model, survival rates were comparable between wild-type strain-infected and ccs4 mutant strain-infected mice, while the ccs4 mutant strain exhibited a lower level of virulence in the intravenous infection model. In addition, at 24 hours after intravenous infection, the bacterial burden in blood was comparable between the wild-type and ccs4 mutant strain-infected mice, whereas the wild-type strain-infected mice showed a significantly higher bacterial burden in the brain. These results suggest that Ccs4 contributes to pneumococcal invasion of host brain tissues and functions as a virulence factor.
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