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Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms
Here, we report the first complete genomes of three cultivable treponeme species from bovine digital dermatitis (DD) skin lesions, two comparative human treponemes, considered indistinguishable from bovine DD species, and a bovine gastrointestinal (GI) treponeme isolate. Key genomic differences betw...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049484/ https://www.ncbi.nlm.nih.gov/pubmed/33780514 http://dx.doi.org/10.1371/journal.ppat.1009464 |
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author | Staton, Gareth J. Clegg, Simon R. Ainsworth, Stuart Armstrong, Stuart Carter, Stuart D. Radford, Alan D. Darby, Alistair Wastling, Jonathan Hall, Neil Evans, Nicholas J. |
author_facet | Staton, Gareth J. Clegg, Simon R. Ainsworth, Stuart Armstrong, Stuart Carter, Stuart D. Radford, Alan D. Darby, Alistair Wastling, Jonathan Hall, Neil Evans, Nicholas J. |
author_sort | Staton, Gareth J. |
collection | PubMed |
description | Here, we report the first complete genomes of three cultivable treponeme species from bovine digital dermatitis (DD) skin lesions, two comparative human treponemes, considered indistinguishable from bovine DD species, and a bovine gastrointestinal (GI) treponeme 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, worldwide disease. Bovine DD treponemes have additional oxidative stress genes compared to nearest human-isolated relatives, suggesting better oxidative stress tolerance, and potentially explaining how bovine strains can colonize skin surfaces. Comparison of both 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 production of 2,3-diacetamido-2,3-dideoxy-d-mannuronic acid, a rare di-N-acetylated mannuronic acid sugar, as important for pathogenesis. Bovine T. phagedenis strains further differed from human strains by having unique genetic clusters including components of a type IV secretion system and a phosphate utilisation system including phoU, a gene associated with 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 exhibiting enhanced survival. This novel mechanism could enable a selective advantage, allowing environmental persistence and transmission of bovine T. phagedenis. Finally, we investigated putative outer membrane protein (OMP) ortholog families across the DD treponemes and identified several families as multi-specific adhesins capable of binding extra cellular matrix (ECM) components. One bovine pathogen specific adhesin ortholog family showed considerable serodiagnostic potential with the Treponema medium representative demonstrating considerable 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. |
format | Online Article Text |
id | pubmed-8049484 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-80494842021-04-28 Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms Staton, Gareth J. Clegg, Simon R. Ainsworth, Stuart Armstrong, Stuart Carter, Stuart D. Radford, Alan D. Darby, Alistair Wastling, Jonathan Hall, Neil Evans, Nicholas J. PLoS Pathog Research Article Here, we report the first complete genomes of three cultivable treponeme species from bovine digital dermatitis (DD) skin lesions, two comparative human treponemes, considered indistinguishable from bovine DD species, and a bovine gastrointestinal (GI) treponeme 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, worldwide disease. Bovine DD treponemes have additional oxidative stress genes compared to nearest human-isolated relatives, suggesting better oxidative stress tolerance, and potentially explaining how bovine strains can colonize skin surfaces. Comparison of both 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 production of 2,3-diacetamido-2,3-dideoxy-d-mannuronic acid, a rare di-N-acetylated mannuronic acid sugar, as important for pathogenesis. Bovine T. phagedenis strains further differed from human strains by having unique genetic clusters including components of a type IV secretion system and a phosphate utilisation system including phoU, a gene associated with 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 exhibiting enhanced survival. This novel mechanism could enable a selective advantage, allowing environmental persistence and transmission of bovine T. phagedenis. Finally, we investigated putative outer membrane protein (OMP) ortholog families across the DD treponemes and identified several families as multi-specific adhesins capable of binding extra cellular matrix (ECM) components. One bovine pathogen specific adhesin ortholog family showed considerable serodiagnostic potential with the Treponema medium representative demonstrating considerable 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. Public Library of Science 2021-03-29 /pmc/articles/PMC8049484/ /pubmed/33780514 http://dx.doi.org/10.1371/journal.ppat.1009464 Text en © 2021 Staton et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Staton, Gareth J. Clegg, Simon R. Ainsworth, Stuart Armstrong, Stuart Carter, Stuart D. Radford, Alan D. Darby, Alistair Wastling, Jonathan Hall, Neil Evans, Nicholas J. Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms |
title | Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms |
title_full | Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms |
title_fullStr | Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms |
title_full_unstemmed | Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms |
title_short | Dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms |
title_sort | dissecting the molecular diversity and commonality of bovine and human treponemes identifies key survival and adhesion mechanisms |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049484/ https://www.ncbi.nlm.nih.gov/pubmed/33780514 http://dx.doi.org/10.1371/journal.ppat.1009464 |
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