Combining genomics and epidemiology to analyse bi-directional transmission of Mycobacterium bovis in a multi-host system

Crispell, Joseph; Benton, Clare H.; Balaz, Daniel; Maio, Nicola De; Ahkmetova, Assel; Allen, Adrian; Biek, Roman; Presho, Eleanor; Dale, James; Hewinson, R. Glyn; Lycett, Samantha; Nuñéz-García, Javier; Skuce, Robin; Trewby, Hannah; Wilson, Daniel J.; Zadoks, Ruth N.; Delahay, Richard J.; Kao, Rowland R.

doi:10.7554/elife.45833

Cited by 81 publications

(148 citation statements)

References 85 publications

(126 reference statements)

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…However, as in the previous reports, this study could not determine the direction(s) of transmission between the two species. Recent work 17 suggests that analysis of whole genome sequence data from badger and cattle isolates in the same geographical locations might allow a better quantification of the roles of badgers and cattle in any inter-species transmission. The authors' findings suggested that in Woodchester Park, England, within species transmission occurred at higher rates than between species transmission and that transmission occurred more frequently from badgers to cattle than vice versa.…”

Section: Discussionmentioning

confidence: 99%

Temporal and spatial Mycobacterium bovis prevalence patterns as evidenced in the All Wales Badgers Found Dead (AWBFD) survey of infection 2014–2016

Schroeder¹,

Hopkins

Galloway³

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

In order to better understand the spatial spread of bovine tuberculosis (bTB) in Wales, an All Wales Badgers Found Dead (AWBFD) survey was carried out from 2014–2016. For Wales, as a whole, there was a significant decrease (p < 0.001) in prevalence of bTB in badgers since a similar survey was carried out in 2005–2006, with a drop from 13.3% to 7.3%. The highest prevalence was observed for the High TB Area East (18.6%), which shares its border with England, and differed significantly (p < 0.001) from the High TB Area West (7.4%). The lowest proportion of carcases diagnosed with the disease (0.7%) was in the Low TB Area, followed by the two Intermediate TB Areas of Wales (2.7%). The M. bovis isolates from badgers tended to be similar to the genotypes of cattle in the same area, except in the Low TB Area. The direction of any cross species transmission and the drivers for this cannot be determined from this study. The spatial variations described here support the need for regionally adapted surveillance and control measures for bovine tuberculosis in Wales.

show abstract

Section: Discussionmentioning

confidence: 99%

Temporal and spatial Mycobacterium bovis prevalence patterns as evidenced in the All Wales Badgers Found Dead (AWBFD) survey of infection 2014–2016

Schroeder¹,

Hopkins

Galloway³

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Post-mortem investigations have revealed progressive disease in some infected badgers with the potential to shed bacteria [23], and longitudinal sampling of live animals suggests the existence of a sub-group that persistently shed from multiple sources [24]. Both epidemiological field studies [24] and molecular typing [4] provide evidence for the persistence and transmission of infection amongst badgers, which is consistent with their role as a maintenance host. Although increases in their abundance may have contributed to the emergence of wild hosts as significant players in the epidemiology of TB, the risk of transmission to cattle posed by each host species is also related to the number of viable mycobacteria excreted [21,24] and to behavioral, ecological, and farm management factors [6,7,25], which determine rates of direct and indirect contact with wildlife [2].…”

Section: Discussionmentioning

confidence: 68%

“…Evidence for TB maintenance in multi-host systems in Europe arises from molecular epidemiological studies demonstrating inter-species transmission between cattle, non-bovine domestic species, and wildlife [4,5]; observational studies reporting TB in domestic and wild animals as a risk factor for cattle [6,7]; and case reports of inter-species transmission [8]. Experimental studies have demonstrated the inter-species transmission of M. bovis under controlled and natural conditions [9,10].…”

Section: Introductionmentioning

confidence: 99%

Quantification of the Animal Tuberculosis Multi-Host Community Offers Insights for Control

et al. 2020

View full text Add to dashboard Cite

Animal tuberculosis (TB) is a multi-host zoonotic disease whose prevalence in cattle herds in Europe has been increasing, despite a huge investment in eradication. The composition of the host community is a fundamental driver of pathogen transmission, and yet this has not been formally quantified for animal TB in Europe. We quantified multi-host communities of animal TB, using stochastic models to estimate the number of infected domestic and wild hosts in three regions: officially TB-free Central–Western Europe, and two largely TB-endemic regions, the Iberian Peninsula and Britain and Ireland. We show that the estimated number of infected animals in the three regions was 290,059–1,605,612 and the numbers of infected non-bovine domestic and wild hosts always exceeded those of infected cattle, with ratios ranging from 3.3 (1.3–19.6):1 in Britain and Ireland to 84.3 (20.5–864):1 in the Iberian Peninsula. Our results illustrate for the first time the extent to which animal TB systems in some regions of Europe are dominated by non-bovine domestic and wild species. These findings highlight the need to adapt current strategies for effective future control of the disease.

show abstract

“…We calculated the Consistency Index for all positions on the E. coli reference chromosome. A low Consistency Index value for a position indicates a high degree of inconsistency with the chromosomal phylogeny and can be calculated by HomoplasyFinder as described in earlier studies [10,39,40]. As can be observed in Figure 3 isolates categorized as a low-level AmpC producer (no pampC gene and no known ampC promoter mutation) tested CTX resistant and contained an insertion in the spacer region (-16_-15insT), which has not been described by Tracz et al [6].…”

Section: Genomic Homoplastic Mutationsmentioning

confidence: 87%

Genome-wide analysis inEscherichia coliunravels an unprecedented level of genetic homoplasy associated with cefotaxime resistance

Coolen¹,

Drijver

Verweij

et al. 2020

Preprint

View full text Add to dashboard Cite

ABSTRACTCefotaxime (CTX) is a commonly used third-generation cephalosporin (3GC) to treat infections caused by Escherichia coli. Two genetic mechanisms have been associated with 3GC resistance in E. coli. The first is the conjugative transfer of a plasmid harboring antibiotic resistance genes. The second is the introduction of mutations in the promoter region of the ampC β-lactamase gene that cause chromosomal-encoded β-lactamase hyperproduction. A wide variety of promoter mutations related to AmpC hyperproduction have been described. However, their link to a specific 3GC such as CTX resistance has not been reported. Here, we measured CTX MICs in 172 cefoxitin resistant E. coli isolates and performed genome-wide analysis of homoplastic mutations associated with CTX resistance by comparing Illumina whole-genome sequencing data of all isolates to a PacBio tailored-made reference chromosome. We mapped the mutations on the reference chromosome and determined their occurrence in the phylogeny, revealing extreme homoplasy at the −42 position of the ampC promoter. The 24 occurrences of a “T” at the −42 position rather than the wild type “C”, resulted from 18 independent C>T mutations in 5 phylogroups. The −42 C>T mutation was only observed in E. coli lacking a plasmid-encoded ampC gene. The association of the −42 C>T mutation with CTX resistance was confirmed to be significant (FDR < 0.05). To conclude, genome-wide analysis of homoplasy in combination with CTX resistance identifies the −42 C>T mutation of the ampC promotor as significantly associated with CTX resistance and underline the role of recurrent mutations in the spread of antibiotics resistance.Impact StatementIn the past decades, the worldwide spread of extended spectrum beta-lactamases (ESBLs) has led to a substantial increase in the prevalence of resistant common pathogens, thereby restricting available treatment options. Although acquired resistance genes, e.g. ESBLs, get most attention, chromosome-encoded resistance mechanisms may play an important role as well. In E. coli chromosome-encoded β-lactam resistance can be caused by alterations in the promoter region of the ampC gene. To improve our understanding of how frequently these alterations occur, a comprehensive interpretation of the evolution of these mutations is essential. This study is the first to apply genome-wide homoplasy analysis to better perceive adaptation of the E. coli genome to antibiotics. Thereby, this study grants insights into how chromosomal-encoded antibiotic resistance evolves and, by combining genome-wide association studies with homoplasy analyses, provides potential strategies for future association studies into the causes of antibiotics resistance.Data summaryAll data is available under BioProject: PRJNA592140. Raw Illumina sequencing data and metadata of all 171 E. coli isolates used in this study is available from the Sequence Read Archive database under accession no. SAMN15052485 to SAMN15052655. Full reference chromosome of ampC_0069 is available via GenBank accession no. CP046396.1 and NCBI Reference Sequence: NZ_CP046396.1.

show abstract

Combining genomics and epidemiology to analyse bi-directional transmission of Mycobacterium bovis in a multi-host system

Cited by 81 publications

References 85 publications

Temporal and spatial Mycobacterium bovis prevalence patterns as evidenced in the All Wales Badgers Found Dead (AWBFD) survey of infection 2014–2016

Temporal and spatial Mycobacterium bovis prevalence patterns as evidenced in the All Wales Badgers Found Dead (AWBFD) survey of infection 2014–2016

Quantification of the Animal Tuberculosis Multi-Host Community Offers Insights for Control

Genome-wide analysis inEscherichia coliunravels an unprecedented level of genetic homoplasy associated with cefotaxime resistance

Contact Info

Product

Resources

About