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Published on: February 23, 2014
Comparative Genomic Analysis of Meningitis- and Bacteremia-Causing Pneumococci Identifies a Common Core Genome
Benard W Kulohoma1, Jennifer E Cornick2, Chrispin Chaguza2
1Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom bkulohoma@iscb.org r.heyderman@ucl.ac.uk.
Abstract:
Streptococcus pneumoniae is a nasopharyngeal commensal that occasionally invades normally sterile sites to cause bloodstream infection and meningitis. Although the pneumococcal population structure and evolutionary genetics are well defined, it is not clear whether pneumococci that cause meningitis are genetically distinct from those that do not. Here, we used whole-genome sequencing of 140 isolates of S. pneumoniae recovered from bloodstream infection (n = 70) and meningitis (n = 70) to compare their genetic contents. By fitting a double-exponential decaying-function model, we show that these isolates share a core of 1,427 genes (95% confidence interval [CI], 1,425 to 1,435 genes) and that there is no difference in the core genome or accessory gene content from these disease manifestations. Gene presence/absence alone therefore does not explain the virulence behavior of pneumococci that reach the meninges. Our analysis, however, supports the requirement of a range of previously described virulence factors and vaccine candidates for both meningitis- and bacteremia-causing pneumococci. This high-resolution view suggests that, despite considerable competency for genetic exchange, all pneumococci are under considerable pressure to retain key components advantageous for colonization and transmission and that these components are essential for access to and survival in sterile sites.
Insights
Meningitis-causing Streptococcus pneumoniae are not genetically distinct from bloodstream infection strains. Whole-genome sequencing reveals no significant differences in core or accessory genes between these disease manifestations.
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- Streptococcus pneumoniae is a common bacterium found in the nasopharynx.
- It can cause severe invasive diseases like meningitis and bloodstream infections.
- Genetic differences between pneumococci causing meningitis versus bloodstream infections are not well understood.
Purpose of the Study:
- To investigate if Streptococcus pneumoniae strains causing meningitis are genetically distinct from those causing bloodstream infections.
- To compare the whole-genome content of isolates from these two distinct disease manifestations.
Main Methods:
- Whole-genome sequencing was performed on 140 Streptococcus pneumoniae isolates.
- 70 isolates were from bloodstream infections and 70 were from meningitis cases.
- A double-exponential decaying-function model was used to analyze core and accessory genome content.
Main Results:
- A core genome of 1,427 genes was identified across all isolates.
- No significant differences were found in core or accessory gene content between meningitis and bloodstream infection isolates.
- The presence or absence of genes does not solely explain pneumococcal virulence in meningitis.
Conclusions:
- Gene content alone does not differentiate pneumococci causing meningitis from those causing bloodstream infections.
- Both disease types require previously identified virulence factors and vaccine targets.
- Pneumococci maintain essential genes for colonization and transmission despite genetic exchange capabilities, crucial for invasive disease.
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