Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Streptococcus pneumoniae Ccs4 involved in penetration across blood-brain barrier and virulence in meningitis (#159)

Yujiro Hirose 1 , Masaya Yamaguchi 1 , Kana Goto 1 , Tomoko Sumitomo 1 , Masanobu Nakata 1 , Shigetada Kawabata 1
  1. Osaka University Graduate School of Dentistry, Suita, OSAKA, Japan

 Streptococcus pneumoniae is a pathogen known to be a leading cause of pneumonia, sepsis, and meningitis. Although ccs4, encoding candidate combox site 4, has been reported as a late competence gene, its function remains unknown. We examined the role of pneumococcal Ccs4 in the pathogenesis of S. pneumoniae-induced disease.

 We constructed a ccs4 deletion mutant of S. pneumoniae TIGR4 and the mutant strain complemented with a shuttle vector harboring Ccs4. Despite prediction that Ccs4 possesses the positively charged extracellular region, susceptibility to LL-37 was comparable among strains. In addition, Ccs4 deletion had no effect on pneumococcal survival in mouse blood. On the other hand, wild-type and complemented strains exhibited significantly higher rates of association and invasion to human brain microvascular endothelial cells as compared to the ccs4 mutant strain. Additionally, we investigated the role of Ccs4 in vivo. In an intravenous infection model, ccs4 mutant strain-infected mice showed prolonged survival, whereas there were no differences seen in an intranasal infection model. Moreover, we examined bacterial burden in brain and blood samples obtained 24 hours after the intravenous infection. Wild-type strain-infected mice showed a significantly higher bacterial burden in the brain as compared to the mutant strain-infected mice, whereas that in blood was comparable between those strains. The median ratio of brain/blood colony forming units of the wild-type strain was also significantly higher than that of the ccs4 mutant strain.

 These results indicated that Ccs4 is involved in pneumococcal penetration across the blood-brain barrier and contributes to its virulence.