title: Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis.
abstract: Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African 'meningitis belt' and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution.
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Mustapha M
authors.initials: MM
authors.lastname: Mustapha
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Jane W
authors.initials: JW
authors.lastname: Marsh
authors.affiliation: Public Health Dynamics Laboratory, Graduate School of Public Health, University of Pittsburgh, USA.
authors.forename: Mary G
authors.initials: MG
authors.lastname: Krauland
authors.affiliation: Molecular Genetics Laboratory, Public Health Institute of Chile, Santiago, Chile.
authors.forename: Jorge O
authors.initials: JO
authors.lastname: Fernandez
authors.affiliation: Department of Bacteriology, Instituto Adolfo Lutz (IAL), São Paulo, Brazil.
authors.forename: Ana Paula S
authors.initials: AP
authors.lastname: de Lemos
authors.affiliation: The Institute for Genome Sciences, University of Maryland School of Medicine, University of Maryland, Baltimore, MD, USA.
authors.forename: Julie C
authors.initials: JC
authors.lastname: Dunning Hotopp
authors.affiliation: Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Meningitis and Vaccine Preventable Diseases Branch, Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Mayer
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Lawrence
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.
authors.forename: N Luisa
authors.initials: NL
authors.lastname: Hiller
authors.affiliation: Infectious Diseases Epidemiology Research Unit, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Lee H
authors.initials: LH
authors.lastname: Harrison
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D004196:Disease Outbreaks; D005798:Genes, Bacterial; D016679:Genome, Viral; D023281:Genomics; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008585:Meningitis, Meningococcal / Q000453:epidemiology* / Q000382:microbiology*; D058977:Molecular Sequence Annotation; D009345:Neisseria meningitidis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D016366:Open Reading Frames; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D065288:Serogroup; D014774:Virulence / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial
keywords: FHbp; Hajj clone; Invasive meningococcal disease; Virulence factors; W135; Whole genome sequencing