No innocent bystanders: pertussis vaccination epitomizes evolutionary parallelisms betweenBordetella parapertussisandB. pertussis

Abstract

ABSTRACTPathogens adapting to the human host and to vaccination-induced immunity may follow parallel evolutionary paths.Bordetella parapertussis(Bpp) contributes significantly to the burden of whooping cough (pertussis), shares vaccine antigens withBordetella pertussis (Bp),and both pathogens are phylogenetically related and ecological competitors.Bpvaccine antigen-coding genes have accumulated variation, including pertactin disruptions, after introduction of acellular vaccines in the 1990s. We aimed to evaluate evolutionary parallelisms inBpp, even though pertussis vaccines were designed againstBp.We investigated the temporal evolution ofBppsublineages, by sequencing 242Bppisolates collected in France, the USA and Spain between 1937 and 2019, spanning pre-vaccine and two vaccines eras.We estimated the evolutionary rate ofBppat 2.12×10−7substitutions per site·year-1, with a most recent common ancestor of all sequenced isolates around year 1877, and found that pertactin deficiencyin Bppwas driven by 18 disruptive mutations, including deletionprn:ΔG-1895 estimated to have occurred around 1998 and observed in 73.8% (149/202) of post-2007 isolates. In addition, we detected two mutations in thebvgA-fhaBintergenic region (controlling expression of the master transcriptional regulator BvgA and the filamentous hemagglutinin), that became fixed in the early 1900s.Our findings suggest early adaptation ofBppto humans through modulation of thebvgASregulon, and a rapid adaptation through the loss of pertactin expression, representing a late evolutionary parallelism concomitant with acellular vaccination against whooping cough.IMPORTANCEVaccination againstBordetella pertussis(Bp) has strongly affected the recent evolution of this main agent of whooping cough. Whether it may have done so co-incidentally onBordetella parapertussis(Bpp), which is genetically and ecologically very similar toBp,has not been described in detail. Our findings show striking evolutionary parallelisms ofBppwithBp, including early changes in a critical regulatory region, and strong evidence of adaptation to vaccine-driven population immunity, even though whooping cough vaccines were not designed explicitly againstBpp. The rapid populational loss of pertactin in countries where acellular pertussis vaccines are used may also reduce protection by vaccination againstBpp, the second agent of whooping cough.