title: Comparative Genomic Analysis of Meningitis- and Bacteremia-Causing Pneumococci Identifies a Common Core Genome.
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.
authors.affiliation: Malawi-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.
authors.forename: Benard W
authors.initials: BW
authors.lastname: Kulohoma
authors.affiliation: Malawi-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.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cornick
authors.affiliation: Malawi-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.
authors.forename: Chrispin
authors.initials: C
authors.lastname: Chaguza
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Feyruz
authors.initials: F
authors.lastname: Yalcin
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Gray
authors.affiliation: Malawi-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.
authors.forename: Anmol M
authors.initials: AM
authors.lastname: Kiran
authors.affiliation: University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Molyneux
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: French
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Julian
authors.identifier: http://orcid.org/0000-0002-7069-5958
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Faragher
authors.affiliation: Malawi-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.
authors.forename: Dean B
authors.initials: DB
authors.lastname: Everett
authors.affiliation: Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi bkulohoma@iscb.org r.heyderman@ucl.ac.uk.
authors.forename: Robert S
authors.identifier: http://orcid.org/0000-0003-4573-449X
authors.initials: RS
authors.lastname: Heyderman
mesh_terms: D016470:Bacteremia / Q000382:microbiology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D008581:Meningitis / Q000382:microbiology*; D013290:Streptococcal Infections / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins