Biology subjects

Crispell, J.

Publications and source records attributed to Crispell, J..

4 recordsLinked to original sources

bioRxiv2021

Genomic epidemiology of Mycobacterium bovis infection in sympatric badger and cattle populations in Northern Ireland.

BackgroundBovine tuberculosis (bTB) is a costly, epidemiologically complex, multi-host, endemic disease. Pathogen whole genome sequencing can improve the resolution of epidemiological tracing. We genome sequenced an exceptional data set of 619 Mycobacterium bovis isolates from badgers and cattle in a 100km2 bTB hotspot. Historical molecular subtyping data permitted the targeting of an endemic pathogen lineage, whose long-term persistence provided an opportunity to study genome epidemiology in detail. To assess whether badger population genetic structure was associated with the spatial distribution of pathogen genetic diversity, we microsatellite genotyped hair samples from 769 badgers trapped in this area. ResultsEight lineages of M. bovis were circulating in the study area, seven of which were likely non-endemic, and imported by animal movement. The endemic lineage exhibited low genetic diversity with an average inter-isolate genetic distance of 7.6 SNPs (s.d. {+/-} 4.0), consistent with contemporary transmission. Bayesian phylogenetic methods determined an evolutionary rate of 0.30 substitutions per genome per year for this lineage, estimating its emergence 40-50 years before present, while Bayesian Skyline analysis identified significant population expansion of the endemic lineage in the 1990s and again in 2011-2012. The phylogeny revealed distinct sub-lineages, all of which contained isolates from both cattle and badger hosts, indicative of the sharing of closely related strains and inter-species transmission. However, the presence of significant badger population genetic structure was not associated with the spatial distribution of M. bovis genetic diversity. ConclusionsOur data provided unparalleled detail on the evolutionary history of an endemic M. bovis lineage. Findings are consistent with ongoing interspecies transmission in the study area but suggest that badger intra-species transmission may not be a major driver of persistence in this area. In addition, the data collected permitted the tracking of incursions of novel pathogen lineages into the study area and means to determine if they were involved in disease transmission.

evolutionary biology↗

bioRxiv2020

Phylodynamic analysis of an emergent Mycobacterium bovis outbreak in an area with no previously known wildlife infections

Understanding how an emergent pathogen successfully establishes itself and persists in a previously unaffected population is a crucial problem in disease ecology. In multi-host pathogen systems this problem is particularly difficult, as the importance of each host species to transmission is often poorly characterised, and the epidemiology of the disease is complex. Opportunities to observe and analyse such emergent scenarios are few. Here, we exploit a unique dataset combining densely-collected data on the epidemiological and evolutionary characteristics of an outbreak of Mycobacterium bovis (M. bovis, the causative agent of bovine tuberculosis, bTB) in a population of cattle and badgers in an area considered low-risk for bTB, that has no previous record of either persistent infection in cattle, or of any infection in wildlife. We analyse the outbreak dynamics using a combination of mathematical modelling, machine learning and Bayesian evolutionary analyses. Comparison to M. bovis whole-genome sequences from Northern Ireland confirmed this to be a single introduction of the pathogen from the latter region, with evolutionary analysis supporting an introduction directly into the local cattle population at least six years prior to its first discovery in badgers. Once introduced, the evidence supports M. bovis epidemiological dynamics passing through two phases, the first dominated by cattle-to-cattle transmission before becoming established in the local badger population. These findings emphasise the importance of disease surveillance for early containment of outbreaks, in particular for pathogens not causing immediately evident symptoms in the infected host, and highlight the utility of combining dynamic modelling and phylogenetic analyses for understanding the often complex infection dynamics associated with emergent outbreaks.

ecology↗

bioRxiv2020

Identifying likely transmission pairs with pathogen sequence data using Kolmogorov Forward Equations; an application to M.bovis in cattle and badgers

Established methods for whole-genome-sequencing (WGS) technology allow for the detection of single-nucleotide polymorphisms (SNPs) in the pathogen genomes sourced from host samples. The information obtained can be used to track the pathogens evolution in time and potentially identify who-infected-whom with unprecedented accuracy. Successful methods include phylodynamic approaches that integrate evolutionary and epidemiological data. However, they are typically computationally intensive, require extensive data, and are best applied when there is a strong molecular clock signal and substantial pathogen diversity. To determine how much transmission information can be inferred when pathogen genetic diversity is low and metadata limited, we propose an analytical approach that combines pathogen WGS data and sampling times from infected hosts. It accounts for between-scale processes, in particular within-host pathogen evolution and between-host transmission. We applied this to a well-characterised population with an endemic Mycobacterium bovis (the causative agent of bovine/zoonotic tuberculosis, bTB) infection. Our results show that, even with such limited data and low diversity, the computation of the transmission probability between host pairs can help discriminate between likely and unlikely infection pathways and therefore help to identify potential transmission networks, but can be sensitive to assumptions about within-host evolution.

ecology↗

bioRxiv2019

Updated functional annotation of the Mycobacterium bovis AF2122/97 reference genome.

Mycobacterium bovis AF2122/97 is the reference strain for the bovine tuberculosis bacillus. We here report an update to the M. bovis AF2122/97 genome annotation to reflect 616 new protein identifications which replace many of the old hypothetical coding sequences and proteins of unknown function in the genome. These changes integrate information from functional assignments of orthologous coding sequences in the Mycobacterium tuberculosis H37Rv genome. We have also added 69 additional new gene names.

microbiology↗