Abstract
Background The re-emergence of whooping cough and geographic disparities in vaccine escape or antimicrobial resistance dynamics, underline the importance of a unified definition of Bordetella pertussis strains. Understanding of the evolutionary adaptations of Bordetella pathogens to humans and animals requires comparative studies with environmental bordetellae.
Methods We have set-up a unified library of Bordetella genomes by merging previously existing Oxford and Pasteur databases, importing genomes from public repositories, and developing harmonized genotyping schemes. We developed a genus-wide cgMLST genotyping scheme and incorporated a previous B. pertussis cgMLST scheme. Specific schemes were developed to define antigenic, virulence and macrolide resistance profiles. Genomic sequencing of 83 French B. bronchiseptica isolates and of B. tumulicola, B. muralis and B. tumbae type strains was performed.
Results The public library currently includes 2,581 Bordetella isolates and their provenance data, and 2,084 genomes. The “classical Bordetella” (B. bronchiseptica, B. parapertussis and B. pertussis), which form a single genomic species (B. bronchiseptica genomic species, BbGS), were overrepresented (n=2,382). The phylogenetic analysis of Bordetella genomes associated the three novel species B. tumulicola, B. muralis and B. tumbae in a clade with B. petrii and revealed 18 yet undescribed species. A sister lineage of the classical bordetellae, provisionally named Bbs lineage II, was uncovered and may represent a novel species (average nucleotide identity with BbGS strains: ∼95%). It comprised strain HT200 from India, two strains of ‘genogroup 6’ from the USA and six clinical isolates from France; this lineage lacked ptxP and its fim2 gene was divergent. Within B. pertussis, vaccine antigen sequence types marked important phylogenetic subdivisions, and macrolide resistance markers (23S_rRNA allele 13 and fhaB3) confirmed the current restriction of this phenotype in China with few exceptions.
Conclusions The genomic platform provides an expandable resource for unified genotyping of Bordetella strains and will facilitate collective evolutionary and epidemiological understanding of the re-emergence of whooping cough and other Bordetella infections.
Data summary Bordetella genomes list and accession numbers: Supplementary Table S4
Bordetella genus phylogeny dataset (92 isolates): https://bigsdb.pasteur.fr/cgi-bin/bigsdb/bigsdb.pl?db=pubmlst_bordetella_isolates&page=query&project_list=23&submit=1
B. bronchiseptica phylogeny dataset (213 isolates): https://bigsdb.pasteur.fr/cgi-bin/bigsdb/bigsdb.pl?db=pubmlst_bordetella_isolates&page=query&project_list=24&submit=1
B. pertussis phylogeny (124 isolates): https://bigsdb.pasteur.fr/cgi-bin/bigsdb/bigsdb.pl?db=pubmlst_bordetella_isolates&page=query&project_list=25&submit=1
iTOL interactive trees: https://itol.embl.de/shared/1l7Fw0AvKOoCF
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Repositories Sequence reads for Bordetella bronchiseptica isolates from France, and for B. tumulicola, B. muralis and B. tumbae type strains (newly sequenced genomes) have been deposited in the European Nucleotide Archive under BioProject number PRJEB49946.
