Selection and emergence of pertussis toxin promoter ptxP3 allele in the evolution of Bordetella pertussis

Evolutionary studies using single nucleotide polymorphisms (SNPs) have separated Bordetella pertussis isolates into six major clusters, with recent isolates forming cluster I. The expansion of cluster I isolates was characterised by changes in genes encoding antigenic components in acellular vaccines, including pertactin (Prn). Here, we determined the initial emergence of the pertussis toxin promoter allele, ptxP3, from an evolutionary perspective. This allele was previously shown in a study from the Netherlands to be associated with increased pertussis toxin production as a result of a single base mutation in the ptxP. The ptxP region of 313 worldwide isolates was sequenced, including 208 isolates from Australia collected over a 40 year period. Eight alleles were identified, of which only two predominated: ptxP1 and ptxP3. One novel allele was also found. ptxP3 was only found in SNP cluster I of B. pertussis and its emergence is concurrent with the change to the non-vaccine prn2 allele. Our results suggest that the globally distributed cluster I of B. pertussis has the ability to evade vaccine induced selection pressure.

► We determine the initial emergence of ptxP3 using SNP-based phylogeny. ► ptxP3 is only associated with currently circulating isolates from SNP-based cluster I. ► The change to ptxP3 is in addition to other antigenic changes. ► Emphasises cluster I isolates are fitter variants in immunised populations.