title: Comparative Genomics of Carriage and Disease Isolates of Streptococcus pneumoniae Serotype 22F Reveals Lineage-Specific Divergence and Niche Adaptation.
abstract: Streptococcus pneumoniae is a major cause of meningitis, sepsis, and pneumonia worldwide. Pneumococcal conjugate vaccines have been part of the United Kingdom's childhood immunization program since 2006 and have significantly reduced the incidence of disease due to vaccine efficacy in reducing carriage in the population. Here we isolated two clones of 22F (an emerging serotype of clinical concern, multilocus sequence types 433 and 698) and conducted comparative genomic analysis on four isolates, paired by Sequence Type (ST) with one of each pair being derived from carriage and the other disease (sepsis). The most compelling observation was of nonsynonymous mutations in pgdA, encoding peptidoglycan N-acetylglucosamine deacetylase A, which was found in the carriage isolates of both ST433 and 698. Deacetylation of pneumococcal peptidoglycan is known to enable resistance to lysozyme upon invasion. Althought no other clear genotypic signatures related to disease or carriage could be determined, additional intriguing comparisons between the two STs were possible. These include the presence of an intact prophage, in addition to numerous additional phage insertions, within the carriage isolate of ST433. Contrasting gene repertoires related to virulence and colonization, including bacteriocins, lantibiotics, and toxin--antitoxin systems, were also observed.
authors.affiliation: Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Cleary
authors.affiliation: Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Vanessa T
authors.initials: VT
authors.lastname: Devine
authors.affiliation: Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Johanna M C
authors.initials: JM
authors.lastname: Jefferies
authors.affiliation: Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton Foundation NHS Trust, Southampton, United Kingdom Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, United Kingdom.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Webb
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Gladstone
authors.affiliation: Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton Foundation NHS Trust, Southampton, United Kingdom NIHR Southampton Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.affiliation: Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom Institute for Life Sciences, University of Southampton, Southampton, United Kingdom Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton Foundation NHS Trust, Southampton, United Kingdom NIHR Southampton Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Clarke
mesh_terms: D000581:Amidohydrolases / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002648:Child; D004352:Drug Resistance, Microbial; D005260:Female; D016680:Genome, Bacterial; D044404:Genomic Islands; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D037521:Virulence Factors; D000581:Amidohydrolases; C411846:pgdA protein, Streptococcus pneumoniae
keywords: Streptococcus pneumoniae; genome sequencing; invasive pneumococcal disease