Dissecting bacteriophage:treponeme interactions to develop novel therapeutics for bovine digital dermatitis

Summary:
Bovine digital dermatitis (BDD) is an infectious lameness in dairy cattle worldwide caused by severe foot lesions. The disease is extremely painful and has considerable economic and food security implications including reduced milk yield and reproduction, costing the UK alone £74 Million/year. Treponemes are considered BDD causal agents and the University of Liverpool (UoL) has been responsible for isolation/characterisation of a large panel of isolates (180+).
With BBSRC RM funding we completed BDD treponeme genomes and proteomes and identified survival/pathogenesis mechanisms(1). Despite only a single bacteriophage to date being characterised for Treponema, we have identified evidence of lysogenic phage in treponemal species (unpublished genomic/electron microscope analyses). Furthermore, a range of putative toxin:antitoxin (TA) systems are encoded within BDD treponemes(1), with TA systems recognised as bacteriophage defence mechanisms. Given no comprehensive BDD treatment exists, this project will identify and characterise treponeme bacteriophage given they represent potential therapeutic/control agents.
The project is a BBSRC DTP PhD studentship with specific objectives as follows:
1. To isolate lysogenic bacteriophage from treponemes within the University of Liverpool (UoL) culture collection and to isolate obligately lytic phage from ruminant foot swabs and farm slurry. We will genome sequence and characterise isolated bacteriophage, as well as investigating their specificity.
2. To undertake bacteriophage-host co-evolution experiments to dissect bacteriophage mechanisms of bacterial species specificity.
3. To characterise phage inhibition by treponeme toxin:antitoxin (TA) systems.
4. To develop cocktails of lytic bacteriophage capable of targeting the diverse range of treponemal species involved in BDD.
The above described study should substantially further the understanding of bacteriophage:spirochete interaction as well as resulting in novel treatments beneficial for cattle health.
References:
1) Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms. PLoS Pathog. 2021 Mar 29;17(3):e1009464. doi:10.1371/journal.ppat.1009464.