title: Use of bacterial whole-genome sequencing to investigate local persistence and spread in bovine tuberculosis.
abstract: Mycobacterium bovis is the causal agent of bovine tuberculosis, one of the most important diseases currently facing the UK cattle industry. Here, we use high-density whole genome sequencing (WGS) in a defined sub-population of M. bovis in 145 cattle across 66 herd breakdowns to gain insights into local spread and persistence. We show that despite low divergence among isolates, WGS can in principle expose contributions of under-sampled host populations to M. bovis transmission. However, we demonstrate that in our data such a signal is due to molecular type switching, which had been previously undocumented for M. bovis. Isolates from farms with a known history of direct cattle movement between them did not show a statistical signal of higher genetic similarity. Despite an overall signal of genetic isolation by distance, genetic distances also showed no apparent relationship with spatial distance among affected farms over distances <5 km. Using simulations, we find that even over the brief evolutionary timescale covered by our data, Bayesian phylogeographic approaches are feasible. Applying such approaches showed that M. bovis dispersal in this system is heterogeneous but slow overall, averaging 2 km/year. These results confirm that widespread application of WGS to M. bovis will bring novel and important insights into the dynamics of M. bovis spread and persistence, but that the current questions most pertinent to control will be best addressed using approaches that more directly integrate WGS with additional epidemiological data.
authors.affiliation: Boyd Orr Centre for Population and Ecosystem Health, Institute for Biodiversity Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Trewby
authors.affiliation: School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.affiliation: Veterinary Sciences Division, Agri-Food and Biosciences Institute, Stormont, Belfast, Northern Ireland, UK.
authors.forename: Eleanor L
authors.initials: EL
authors.lastname: Breadon
authors.affiliation: The Roslin Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Lycett
authors.affiliation: Veterinary Sciences Division, Agri-Food and Biosciences Institute, Stormont, Belfast, Northern Ireland, UK.
authors.forename: Tom R
authors.initials: TR
authors.lastname: Mallon
authors.affiliation: Veterinary Sciences Division, Agri-Food and Biosciences Institute, Stormont, Belfast, Northern Ireland, UK.
authors.forename: Carl
authors.initials: C
authors.lastname: McCormick
authors.affiliation: Boyd Orr Centre for Population and Ecosystem Health, Institute for Biodiversity Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Johnson
authors.affiliation: Boyd Orr Centre for Population and Ecosystem Health, Institute for Biodiversity Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Orton
authors.affiliation: Veterinary Sciences Division, Agri-Food and Biosciences Institute, Stormont, Belfast, Northern Ireland, UK.
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Allen
authors.affiliation: Glasgow Polyomics, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Galbraith
authors.affiliation: Glasgow Polyomics, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Pawel
authors.initials: P
authors.lastname: Herzyk
authors.affiliation: School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK; Veterinary Sciences Division, Agri-Food and Biosciences Institute, Stormont, Belfast, Northern Ireland, UK.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Skuce
authors.affiliation: Boyd Orr Centre for Population and Ecosystem Health, Institute for Biodiversity Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK.
authors.forename: Roman
authors.initials: R
authors.lastname: Biek
authors.affiliation: Boyd Orr Centre for Population and Ecosystem Health, Institute for Biodiversity Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK. Electronic address: rowland.kao@glasgow.ac.uk.
authors.forename: Rowland R
authors.initials: RR
authors.lastname: Kao
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D002417:Cattle; D055106:Genome-Wide Association Study; D009163:Mycobacterium bovis / Q000235:genetics*; D014380:Tuberculosis, Bovine / Q000235:genetics* / Q000635:transmission*
keywords: Bacterial evolution; Livestock disease; Molecular epidemiology; Mycobacterium bovis; Phylogeography