title: Insight into evolution of Bordetella pertussis from comparative genomic analysis: evidence of vaccine-driven selection.
abstract: Despite high vaccine coverage, pertussis incidence has increased substantially in recent years in many countries. A significant factor that may be contributing to this increase is adaptation to the vaccine by Bordetella pertussis, the causative agent of pertussis. In this study, we first assessed the genetic diversity of B. pertussis by microarray-based comparative genome sequencing of 10 isolates representing diverse genotypes and different years of isolation. We discovered 171 single nucleotide polymorphisms (SNPs) in a total of 1.4 Mb genome analyzed. The frequency of base changes was estimated as one per 32 kb per isolate, confirming that B. pertussis is one of the least variable bacterial pathogens. We then analyzed an international collection of 316 B. pertussis isolates using a subset of 65 of the SNPs and identified 42 distinct SNP profiles (SPs). Phylogenetic analysis grouped the SPs into six clusters. The majority of recent isolates belonged to clusters I-IV and were descendants of a single prevaccine lineage. Cluster I appeared to be a major clone with a worldwide distribution. Typing of genes encoding acellular vaccine (ACV) antigens, ptxA, prn, fhaB, fim2, and fim3 revealed the emergence and increasing incidence of non-ACV alleles occurring in clusters I and IV, which may have been driven by ACV immune selection. Our findings suggest that B. pertussis, despite its high population homogeneity, is evolving in response to vaccination pressure with recent expansion of clones carrying variants of genes encoding ACV antigens.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Sophie
authors.initials: S
authors.lastname: Octavia
authors.forename: Ram P
authors.initials: RP
authors.lastname: Maharjan
authors.forename: Vitali
authors.initials: V
authors.lastname: Sintchenko
authors.forename: Gordon
authors.initials: G
authors.lastname: Stevenson
authors.forename: Peter R
authors.initials: PR
authors.lastname: Reeves
authors.forename: Gwendolyn L
authors.initials: GL
authors.lastname: Gilbert
authors.forename: Ruiting
authors.initials: R
authors.lastname: Lan
mesh_terms: D005075:Biological Evolution; D001886:Bordetella pertussis / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D055028:Comparative Genomic Hybridization / Q000379:methods*; D019295:Computational Biology; D016680:Genome, Bacterial; D006801:Humans; D010567:Pertussis Vaccine / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D014611:Vaccination; D014917:Whooping Cough / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control
chemical_list: D010567:Pertussis Vaccine