Bordetella pertussis is a strictly human pathogen causing the respiratory infectious disease called whooping cough or pertussis. B. pertussis adaptation to acellular pertussis vaccine pressure has been repeatedly highlighted, but recent data indicate that adaptation of circulating strains started already in the era of the whole cell pertussis vaccine (wP) use. We sequenced the genomes of five B. pertussis wP vaccine strains isolated in the former Czechoslovakia in the pre-wP (1954-1957) and early wP (1958-1965) eras, when only limited population travel into and out of the country was possible. Four isolates exhibit a similar genome organization and form a distinct phylogenetic cluster with a geographic signature. The fifth strain is rather distinct, both in genome organization and SNP-based phylogeny. Surprisingly, despite isolation of this strain before 1966, its closest sequenced relative appears to be a recent isolate from the US. On the genome content level, the five vaccine strains contained both new and already described regions of difference. One of the new regions contains duplicated genes potentially associated with transport across the membrane. The prevalence of this region in recent isolates indicates that its spread might be associated with selective advantage leading to increased strain fitness.

Institute of Microbiology v v i Laboratory of molecular biology of bacterial pathogens 14220 Prague Czech Republic

Institute of Microbiology v v i Laboratory of post transcriptional control of gene expression 14220 Prague Czech Republic

Laboratory for Biotechnology and Bioanalysis Center for Reproductive Biology Washington State University Pullman Washington 99164 7520

University of Vienna Institute for Theoretical Chemistry Währinger Straße 17 A 1090 Vienna Austria

University of Vienna Research group BCB Faculty of Computer Science Währinger Straße 24 1090 Vienna Austria

Wellcome Trust Sanger Institute Wellcome Trust Genome Campus Hinxton CB10 1SA Cambridge UK

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