Genomic dissection of the microevolution of Australian epidemic Bordetella pertussis

ABSTRACT

Whooping cough (pertussis) is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccine coverage, pertussis has re-emerged in many countries including Australia and caused two large epidemics in Australia since 2007. Here, we undertook a genomic and phylogeographic study of 385 Australian B. pertussis isolates collected from 2008 to 2017. The Australian B. pertussis population was found to be composed of mostly ptxP3 strains carrying different fim3 alleles, with ptxP3-fim3A genotype expanding far more than ptxP3-fim3B. Within the former, there were six co-circulating epidemic lineages (EL1 to EL6). The multiple ELs emerged, expanded, and then declined at different time points over the two epidemics. In population genetics terms, both hard and soft selective sweeps through vaccine selection pressures have determined the population dynamics of Australian B. pertussis. Relative risk estimation suggests that once a new B. pertussis lineage emerged, it was more likely to spread locally within the first 1.5 years. However, after 1.5 years, any new lineage was likely to expand to a wider region. Phylogenetic analysis revealed the expansion of ptxP3 strains was also associated with replacement of the type III secretion system allele bscI1 with bscI3. bscI3 is associated with decreased T3SS secretion and may allow B. pertussis to reduce immune recognition. This study advanced our understanding of the epidemic population structure and spatial and temporal dynamics of B. pertussis in a highly immunized population.

KEYWORDS:

• Bordetella pertussis
• re-emergence
• phylogeographic
• global transmission
• evolution

Acknowledgements

We thank Narelle Raven for technical assistance. Z.X. was supported by a University of New South Wales scholarship.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Ruiting Lan conceived the study, Zheng Xu, Dalong Hu and Laurence Luu performed the analysis. Sophie Octavia, Vitali Sintchenko, Frits R. Mooi and Laurence Don Wai Luu revised the manuscript. Mark M. Tanaka supported the calculation of the relative risk. Vitali Sintchenko, Jenny Robson and Anthony D Keil collected B. pertussis isolates. Ruiting Lan provided critical analysis and discussions. All authors discussed the results and contributed to the revision of the final manuscript.

Data availability

All Illumina sequencing reads analysed in this study were deposited in the NCBI database. Raw reads were deposited under the project accession number PRJNA562796. In addition, the other five Illumina sequencing reads collected from 1997 to 2002 were deposited under PRJNA280658 and 78 isolates from 2013 to 2017 Australian epidemic study were deposited under PRJNA432286. The global B. pertussis genomes were downloaded from Sequence Read Archive (SRA) in NCBI by searching “Bordetella pertussis” by the date of 6th Nov 2018.

Additional information

Funding

This work was supported by The National Health and Medical Research Council: [Grant Number 1146938].