Dataset Information

Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis.

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.

SUBMITTER: Hirose Y

PROVIDER: S-EPMC6177246 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis.

Hirose Yujiro Y Yamaguchi Masaya M Goto Kana K Sumitomo Tomoko T Nakata Masanobu M Kawabata Shigetada S

Virulence 20180101 1

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 ...[more]

PMID: 30251911

Similar Datasets

Project description:Streptococcus pneumoniae (pneumococcus) is an opportunistic pathogen that causes otitis media, sinusitis, pneumonia, meningitis and sepsis. The progression to this pathogenic lifestyle is preceded by asymptomatic colonization of the nasopharynx. This colonization is associated with biofilm formation; the competence pathway influences the structure and stability of biofilms. However, the molecules that link the competence pathway to biofilm formation are unknown. Here, we describe a new competence-induced gene, called briC, and demonstrate that its product promotes biofilm development and stimulates colonization in a murine model. We show that expression of briC is induced by the master regulator of competence, ComE. Whereas briC does not substantially influence early biofilm development on abiotic surfaces, it significantly impacts later stages of biofilm development. Specifically, briC expression leads to increases in biofilm biomass and thickness at 72h. Consistent with the role of biofilms in colonization, briC promotes nasopharyngeal colonization in the murine model. The function of BriC appears to be conserved across pneumococci, as comparative genomics reveal that briC is widespread across isolates. Surprisingly, many isolates, including strains from clinically important PMEN1 and PMEN14 lineages, which are widely associated with colonization, encode a long briC promoter. This long form captures an instance of genomic plasticity and functions as a competence-independent expression enhancer that may serve as a precocious point of entry into this otherwise competence-regulated pathway. Moreover, overexpression of briC by the long promoter fully rescues the comE-deletion induced biofilm defect in vitro, and partially in vivo. These findings indicate that BriC may bypass the influence of competence in biofilm development and that such a pathway may be active in a subset of pneumococcal lineages. In conclusion, BriC is a part of the complex molecular network that connects signaling of the competence pathway to biofilm development and colonization.

Project description:BackgroundInvasive pneumococcal disease declined among children and adults after the introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, but its effect on pneumococcal meningitis is unclear.MethodsWe examined trends in pneumococcal meningitis from 1998 through 2005 using active, population-based surveillance data from eight sites in the United States. Isolates were grouped into PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV7-related serotypes (6A, 9A, 9L, 9N, 18A, 18B, 18F, 19B, 19C, 23A, and 23B), and non-PCV7 serotypes (all others). Changes in the incidence of pneumococcal meningitis were assessed against baseline values from 1998-1999.ResultsWe identified 1379 cases of pneumococcal meningitis. The incidence declined from 1.13 cases to 0.79 case per 100,000 persons between 1998-1999 and 2004-2005 (a 30.1% decline, P<0.001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P<0.001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P<0.001) among patients of all ages. Although rates of PCV7-related-serotype disease decreased by 32.1% (P=0.08), rates of non-PCV7-serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P<0.001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P=0.01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P=0.03).ConclusionsRates of pneumococcal meningitis have decreased among children and adults since PCV7 was introduced. Although the overall effect of the vaccine remains substantial, a recent increase in meningitis caused by non-PCV7 serotypes, including strains nonsusceptible to antibiotics, is a concern.

Dataset Information

Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis.

Publications

Competence-induced protein Ccs4 facilitates pneumococcal invasion into brain tissue and virulence in meningitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets