Dissecting the molecular diversity and commonality of bovine digital dermatitis treponemes

We collected entire genome and proteome data for several of these treponemal bacteria considered causal of bovine digital dermatitis (BDD). We also generated genomes for bovine gastrointestinal treponemes and relevant human treponemes and investigated the distribution of relevant virulence factors across the range of treponemes investigated.

Using the genomic data we completed a reverse vaccinology approach identifying a diagnostic antigen and potential vaccine candidates (1).

Further comparative genomic analyses identified production of a novel mannuronic acid sugar as central to BDD treponeme pathogenesis (2). Moreover, relevant survival characteristics were determined which appear to be key to these pathogens surviving on the surface of skin and within the farm environment. Recombinant outer membrane protein generation from key orthologs across the different BDD treponemes determined that most enable host attachment, with considerable functional diversity and redundancy determined (2).

We developed cattle skin fibroblast and keratinocyte models and undertook transcriptomics of cattle skin fibroblasts which had been challenged with the BDD treponemes identifying key inflammatory markers involved in disease pathogenesis (3). Moreover, comparing challenge with pathogenic and commensal treponemes we demonstrated that BDD treponemes appear to be able to immune-evade the host response (3).

These studies have enhanced understanding of the respective pathogens and should allow for future vaccine, diagnostic and treatment studies to better protect from this severe disease of ruminants.

Research outputs

1. Staton, G. J., Carter, S. D., Ainsworth, S., Mullin, J., Smith, R. F., & Evans, N. J. (2020). Putative ß-Barrel Outer Membrane Proteins of the Bovine Digital Dermatitis-Associated Treponemes: Identification, Functional Characterization, and Immunogenicity. Infection and immunity, 88(5). DOI: 10.1128/IAI.00050-20
2. Newbrook, K., Carter, S. D., Crosby-Durrani, H., & Evans, N. J. (2021). Challenge of Bovine Foot Skin Fibroblasts With Digital Dermatitis Treponemes Identifies Distinct Pathogenic Mechanisms. Frontiers in Cellular and Infection Microbiology, 10. DOI: 10.3389/fcimb.2020.538591
3. Staton, G. J., Clegg, S. R., Ainsworth, S., Armstrong, S., Carter, S. D., Radford, A. D., Darby, A., Hall, N., Wastling, J. & Evans, N. J. (2021). Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms. PLOS PATHOGENS, 17(3). DOI: 10.1371/journal.ppat.1009464

Funding

BBSRC RM Grant: Dissecting the molecular diversity and commonality of the bovine digital dermatitis treponemes.  New Investigator Award:  N. Evans (PI), Collaborators: J. Wastling (University of Keele), S. Carter (University of Liverpool) N. Hall (Earlham Institute), A. Darby (University of Liverpool).

BBSRC Studentship: Dissecting host-pathogen interactions in bovine digital dermatitis. Supervisors: N. Evans (Lead) & S. Carter, Student: K. Newbrook.

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