Whole-Genome sequencing in routine Mycobacterium bovis epidemiology – scoping the potential

Adrian Allen*, Ryan Magee, Ryan Devaney, Tara Ardis, Caitlín McNally, Carl McCormick, Eleanor Presho, Michael Doyle, Purnika Ranasinghe, Philip Johnston, Raymond Kirke, Roland Harwood, Damien Farrell, Kevin Kenny, Jordy Smith, Stephen Gordon, Tom Ford, Suzan Thompson, Lorraine Wright, Kerri JonesPaulo Prodohl, Robin Skuce

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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Abstract

Mycobacterium bovis the main agent of bovine tuberculosis (bTB), presents as a series of spatially-localised micro-epidemics across landscapes. Classical molecular typing methods applied to these micro-epidemics, based on genotyping a few variable loci, have significantly improved our understanding of potential epidemiological links between outbreaks. However, they have limited utility owing to low resolution. Conversely, whole-genome sequencing (WGS) provides the highest resolution data available for molecular epidemiology, producing richer outbreak tracing, insights into phylogeography and epidemic evolutionary history. We illustrate these advantages by focusing on a common single lineage of M. bovis (1.140) from Northern Ireland. Specifically, we investigate the spatial sub-structure of 20 years of herd-level multi locus VNTR analysis (MLVA) surveillance data and WGS data from a down sampled subset of isolates of this MLVA type over the same time frame. We mapped 2108 isolate locations of MLVA type 1.140 over the years 2000–2022. We also mapped the locations of 148 contemporary WGS isolates from this lineage, over a similar geographic range, stratifying by single nucleotide polymorphism (SNP) relatedness cut-offs of 15 SNPs. We determined a putative core range for the 1.140 MLVA type and SNP-defined sequence clusters using a 50 % kernel density estimate, using cattle movement data to inform on likely sources of WGS isolates found outside of core ranges. Finally, we applied Bayesian phylogenetic methods to investigate past population history and reproductive number of the 1.140 M. bovis lineage. We demonstrate that WGS SNP-defined clusters exhibit smaller core ranges than the established MLVA type - facilitating superior disease tracing. We also demonstrate the superior functionality of WGS data in determining how this lineage was disseminated across the landscape, likely via cattle movement and to infer how its effective population size and reproductive number has been in flux since its emergence. These initial findings highlight the potential of WGS data for routine monitoring of bTB outbreaks.
Original languageEnglish
Article number001185
Number of pages16
JournalMicrobial Genomics
Volume10
Issue number2
DOIs
Publication statusPublished - 14 Feb 2024

Data Access Statement

All sequence data have been deposited in the European Nucleotide Archive - specifically BioProjects PRJEB65421, PRJNA925930, PRJEB9025.

Code and BEAST XMLs used in the production of this manuscript can be found at the link below:

https://github.com/AdrianAllen1977/Whole_Genome_Sequencing_in_Routine_Mycobacterium_bovis_Epidemiology_Scoping_the_potential.

Locations of cattle herds have been removed from Supplementary Data (available in the online version of this article) to protect personal data.

Keywords

  • Bovine tuberculosis
  • genome epidemiology

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