Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis.
Yujiro HiroseMasaya YamaguchiKana GotoTomoko SumitomoMasanobu NakataShigetada KawabataPublished in: Virulence (2019)
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.
Keyphrases
- wild type
- escherichia coli
- endothelial cells
- pseudomonas aeruginosa
- staphylococcus aureus
- white matter
- resting state
- biofilm formation
- cell migration
- antimicrobial resistance
- genome wide
- type diabetes
- functional connectivity
- risk factors
- high dose
- dna methylation
- wastewater treatment
- diabetic rats
- oxidative stress
- cerebral ischemia
- genome wide identification
- small molecule
- high fat diet induced
- transcription factor
- insulin resistance
- genome wide analysis
- community acquired pneumonia