Abstract

Whooping cough, the respiratory disease caused by Bordetella pertussis , has undergone a wide-spread resurgence over the last several decades. Previously, we developed a pipeline to assemble the repetitive B. pertussis genome into closed sequences using hybrid nanopore and Illumina sequencing. Here, this sequencing pipeline was used to conduct a more high-throughput, longitudinal screen of 66 strains isolated between 1982 and 2018 in New Zealand. New Zealand has a higher incidence of whooping cough than many other countries; usually at least twice as many cases per 100000 people as the USA and UK and often even higher, despite similar rates of vaccine uptake. To the best of our knowledge, these strains are the first New Zealand B. pertussis isolates to be sequenced. The analyses here show that, on the whole, genomic trends in New Zealand B. pertussis isolates, such as changing allelic profile in vaccine-related genes and increasing pertactin deficiency, have paralleled those seen elsewhere in the world. At the same time, phylogenetic comparisons of the New Zealand isolates with global isolates suggest that a number of strains are circulating in New Zealand, which cluster separately from other global strains, but which are closely related to each other. The results of this study add to a growing body of knowledge regarding recent changes to the B. pertussis genome, and are the first genetic investigation into B. pertussis isolates from New Zealand.

Highlights

  • Despite the availability of vaccination, whooping cough, the respiratory disease caused by Bordetella pertussis, has been resurgent in many countries for the past several decades

  • The genomes of 66 isolates from between 1982 and 2018 were sequenced here, using hybrid nanopore and Illumina sequencing, to determine the following: whether global genomic trends observed in B. pertussis had been delayed by New Zealand’s slower vaccine uptake; whether the strains circulating during whooping cough outbreaks were polyclonal, as seen in recent outbreaks in the UK and USA; and whether the consistently higher incidence of whooping cough in New Zealand could potentially be explained by the circulation of a unique hypervirulent strain

  • Allelic profile and antigen deficiency trends in New Zealand generally match those observed elsewhere in the world Analysis of the allelic profile of the acellular pertussis vaccine (ACV)-­related genes in the New Zealand isolates reveals a pattern in the New Zealand strains similar to that seen in Bart et al.’s landmark 2014 study of global strains throughout the 20th and early 21st century, as well as other studies of how B. pertussis populations have changed over recent years [2, 7, 45, 46]

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Summary

Introduction

Despite the availability of vaccination, whooping cough, the respiratory disease caused by Bordetella pertussis, has been resurgent in many countries for the past several decades. Extensive screens of strains circulating during and between epidemics in the UK, Australia and the USA have been conducted in recent years [2,3,4,5,6,7], each contributing to our understanding of how B. pertussis is evolving under selection pressure from vaccines. Key observations from these studies include a shifting allelic profile in many of the genes encoding ACV antigens, such as the pertussis toxin promoter, ptxP. A subsequent study of strains from a 2012 whooping cough outbreak in the UK confirmed that the ACV genes do appear to be mutating at a faster rate than the genes which code for other cell surface proteins [2]

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