Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms

ABSTRACT: Here, we report the first complete genomes of three cultivable treponeme species from bovine digital dermatitis (DD) skin lesions, two comparative human treponemes and a bovine gastrointestinal (GI) isolate. Key genomic differences between bovine and human treponemes implicate microbial mechanisms that enhance knowledge of how DD, a severe disease of ruminants, has emerged into a prolific and endemic disease in countries worldwide. Bovine DD treponemes have additional oxidative stress genes compared to nearest human-isolated relatives, suggesting better toleration of oxidative stress, and thus potentially explaining the ability of bovine strains to colonize skin surfaces. Comparison of bovine DD and GI treponemes as well as bovine pathogenic and human non-pathogenic saprophyte Treponema phagedenis strains indicates genes encoding a five-enzyme biosynthetic pathway for the production of 2,3-diacetamido-2,3-dideoxy-d-mannuronic acid, a rare di-N-acetylated mannuronic acid sugar with potential immunomodulatory activity, as important for pathogenesis. The bovine T. phagedenis strains further differed from human strains by having a larger number of unique genetic features including components of a type IV secretion system and a phosphate utilisation system including phoU, a gene associated with enhanced osmotic stress survival. Proteomic analyses confirmed bovine derived T. phagedenis exhibits expression of PhoU but not the putative secretion system whilst the novel mannuronic acid pathway was expressed in near entirety across the DD treponemes. Analysis of osmotic stress response in water identified a difference between bovine and human T. phagedenis with bovine strains surviving better. This novel mechanism could enable a selective advantage, allowing environmental persistence and transmission of bovine T. phagedenis. Finally, we investigated a range of treponeme genes encoding ortholog families across the DD treponemes representing putative outer membrane proteins (OMPs) and identified several families as multi-specific adhesins capable of binding extra cellular matrix (ECM) components. Human saprophytic T. phagedenis could not be differentiated from bovine pathogenic strains by these adhesins and only two of ten characterised ortholog OMP families were absent from commensal bovine treponemes. One of these bovine pathogen specific adhesin ortholog families showed considerable diagnostic potential with the Treponema medium representative demonstrating the greatest disease specificity (91.6%). This work has shed light on treponeme host adaptation and has identified candidate molecules for future diagnostics, vaccination and therapeutic intervention.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Treponema Ruminis Treponema Phagedenis Treponema Sp. T19 Treponema Sp. T320a Treponema Pedis Treponema Medium

SUBMITTER: Stuart Armstrong  

LAB HEAD: Nicholas Evans

PROVIDER: PXD022419 | Pride | 2021-03-16

REPOSITORIES: Pride