100 years of Bordetella pertussis evolution in the UK

Abstract

The evolution of Bordetella pertussis from its closest ancestors involved the expansion of the copy number of insertion sequence element IS481. Intra-genomic recombination between copies of IS481 has caused extensive genome degradation and structural rearrangements. The first vaccine, a whole-cell vaccine (WCV), for prevention of pertussis disease, also known as whooping cough, was first added to the childhood vaccination programme in the UK in 1951, with the acellular vaccine (ACV) replacing it in 2001. Recent research has suggested that vaccine-mediated selection may be causing waning immunity seen in response to the ACV. However, this research has lacked isolates from the pre-vaccine and WCV eras preventing the full trajectory of recent B. pertussis evolution to be observed. Here, we present a comparison of the whole-genome assemblies of 200 isolates, sequenced using Oxford Nanopore technology, covering a 100-year period in the UK. These isolates cover the pre-vaccine, WCV, and ACV eras to evidence how further genome degradation, structural arrangements, mutations, and allele types of vaccine antigens correlate with a response to vaccine-mediated selection pressure. The balance of gene gain and loss is explored with a pangenome analysis of an additional 924 publicly available closed genomes using the new tool, ggCaller. This gives finer resolution on ‘regions of differences’ previously described in the species, and how these differences correlate to ACV and WCV usage. These regions of difference allude to the genes important in vaccine escape for B. pertussis, which may be an important contributor to declining immunity in countries with ACV use.

Biography

Sarah Cameron is currently a first year PhD student studying the role of copy number variation in antimicrobial resistance at the University of Bath, UK. In 2020, she received her MSc in Molecular Biosciences (Microbiology) and then worked as a research assistant at the University of Oxford developing a high-throughput antibody screen for the Covid-19 infection survey. Sarah, took this knowledge of automation and robotics to the University of Bristol as a specialist technician in a synthetic biology laboratory. She then spent a year as a research assistant in her current laboratory, sequencing and analysing genome rearrangements in Bordetella pertussis.