Comparative genomics of prevaccination and modern Bordetella pertussis strains.
BACKGROUND
Despite vaccination since the 1950s, pertussis has persisted and resurged. It remains a major cause of infant death worldwide and is the most prevalent vaccine-preventable disease in developed countries. The resurgence of pertussis has been associated with the expansion of Bordetella pertussis strains with a novel allele for the pertussis toxin (Ptx) promoter, ptxP3, which have replaced resident ptxP1 strains. Compared to ptxP1 strains, ptxP3 produce more Ptx resulting in increased virulence and immune suppression. To elucidate how B. pertussis has adapted to vaccination, we compared genome sequences of two ptxP3 strains with four strains isolated before and after the introduction vaccination.


RESULTS
The distribution of SNPs in regions involved in transcription and translation suggested that changes in gene regulation play an important role in adaptation. No evidence was found for acquisition of novel genes. Modern strains differed significantly from prevaccination strains, both phylogenetically and with respect to particular alleles. The ptxP3 strains were found to have diverged recently from modern ptxP1 strains. Differences between ptxP3 and modern ptxP1 strains included SNPs in a number of pathogenicity-associated genes. Further, both gene inactivation and reactivation was observed in ptxP3 strains relative to modern ptxP1 strains.


CONCLUSIONS
Our work suggests that B. pertussis adapted by successive accumulation of SNPs and by gene (in)activation. In particular changes in gene regulation may have played a role in adaptation.
Laboratory for Infectious Diseases and Screening, Netherlands Centre for Infectious Diseases Control, RIVM, Bilthoven, Netherlands.
Marieke J
MJ
Bart
Marjolein
M
van Gent
Han G J
HG
van der Heide
Jos
J
Boekhorst
Peter
P
Hermans
Julian
J
Parkhill
Frits R
FR
Mooi
D000483:Alleles; D001886:Bordetella pertussis / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D003062:Codon / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics; D017353:Gene Deletion; D005798:Genes, Bacterial / Q000235:genetics; D023281:Genomics / Q000379:methods*; D016254:Mutagenesis, Insertional / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D010567:Pertussis Vaccine / Q000235:genetics* / Q000276:immunology*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013997:Time Factors; D014611:Vaccination; D014774:Virulence / Q000235:genetics
D003062:Codon; D021901:DNA, Intergenic; D010567:Pertussis Vaccine