title: Whole genome sequencing to investigate the emergence of clonal complex 23 Neisseria meningitidis serogroup Y disease in the United States.
abstract: In the United States, serogroup Y, ST-23 clonal complex Neisseria meningitidis was responsible for an increase in meningococcal disease incidence during the 1990s. This increase was accompanied by antigenic shift of three outer membrane proteins, with a decrease in the population that predominated in the early 1990s as a different population emerged later in that decade. To understand factors that may have been responsible for the emergence of serogroup Y disease, we used whole genome pyrosequencing to investigate genetic differences between isolates from early and late N. meningitidis populations, obtained from meningococcal disease cases in Maryland in the 1990s. The genomes of isolates from the early and late populations were highly similar, with 1231 of 1776 shared genes exhibiting 100% amino acid identity and an average π(N)  =  0.0033 and average π(S)  =  0.0216. However, differences were found in predicted proteins that affect pilin structure and antigen profile and in predicted proteins involved in iron acquisition and uptake. The observed changes are consistent with acquisition of new alleles through horizontal gene transfer. Changes in antigen profile due to the genetic differences found in this study likely allowed the late population to emerge due to escape from population immunity. These findings may predict which antigenic factors are important in the cyclic epidemiology of meningococcal disease.
authors.affiliation: Infectious Diseases Epidemiology Research Unit, School of Medicine and Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvanian, United States of America. mgk8@pitt.edu
authors.forename: Mary G
authors.initials: MG
authors.lastname: Krauland
authors.forename: Julie C
authors.initials: JC
authors.lastname: Dunning Hotopp
authors.forename: David R
authors.initials: DR
authors.lastname: Riley
authors.forename: Sean C
authors.initials: SC
authors.lastname: Daugherty
authors.forename: Jane W
authors.initials: JW
authors.lastname: Marsh
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Messonnier
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Mayer
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
authors.forename: Lee H
authors.initials: LH
authors.lastname: Harrison
mesh_terms: D000483:Alleles; D000942:Antigens, Bacterial / Q000235:genetics*; D002874:Chromosome Mapping; D036781:Fimbriae Proteins / Q000235:genetics; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015994:Incidence; D007501:Iron / Q000378:metabolism; D008589:Meningococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D038581:Neisseria meningitidis, Serogroup Y / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D010802:Phylogeny; D012703:Serotyping; D014481:United States
chemical_list: D000942:Antigens, Bacterial; D036781:Fimbriae Proteins; D007501:Iron