Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche
Abstract Porphyromonas asaccharolytica and Porphyromonas uenonis are common inhabitants of the vaginal microbiome, but their presence has been linked to adverse health outcomes for women, including bacterial vaginosis and preterm birth. However, little is known about the pathogenesis mechanisms of t...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-02-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-022-00270-7 |
| _version_ | 1818988057300303872 |
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| author | Karen V. Lithgow Vienna C. H. Buchholz Emily Ku Shaelen Konschuh Ana D’Aubeterre Laura K. Sycuro |
| author_facet | Karen V. Lithgow Vienna C. H. Buchholz Emily Ku Shaelen Konschuh Ana D’Aubeterre Laura K. Sycuro |
| author_sort | Karen V. Lithgow |
| collection | DOAJ |
| description | Abstract Porphyromonas asaccharolytica and Porphyromonas uenonis are common inhabitants of the vaginal microbiome, but their presence has been linked to adverse health outcomes for women, including bacterial vaginosis and preterm birth. However, little is known about the pathogenesis mechanisms of these bacteria. The related oral opportunistic pathogen, Porphyromonas gingivalis, is comparatively well-studied and known to secrete numerous extracellular matrix-targeting proteases. Among these are the gingipain family of cysteine proteases that drive periodontal disease progression and hematogenic transmission to the placenta. In this study, we demonstrate that vaginal Porphyromonas species secrete broad-acting proteases capable of freely diffusing within the cervicovaginal niche. These proteases degrade collagens that are enriched within the cervix (type I) and chorioamniotic membranes (type IV), as well as fibrinogen, which inhibits clot formation. Bioinformatic queries confirmed the absence of gingipain orthologs and identified five serine, cysteine, and metalloprotease candidates in each species. Inhibition assays revealed that each species’ proteolytic activity can be partially attributed to a secreted metalloprotease with broad substrate specificity that is distantly related to the P. gingivalis endopeptidase PepO. This characterization of virulence activities in vaginal Porphyromonas species highlights their potential to alter the homeostasis of reproductive tissues and harm human pregnancy through clotting disruption, fetal membrane weakening, and premature cervical remodeling. |
| first_indexed | 2024-12-20T19:16:32Z |
| format | Article |
| id | doaj.art-3020de061e1643938c6424c10f0e744f |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-12-20T19:16:32Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-3020de061e1643938c6424c10f0e744f2022-12-21T19:29:05ZengNature Portfolionpj Biofilms and Microbiomes2055-50082022-02-018111510.1038/s41522-022-00270-7Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal nicheKaren V. Lithgow0Vienna C. H. Buchholz1Emily Ku2Shaelen Konschuh3Ana D’Aubeterre4Laura K. Sycuro5Department of Microbiology, Immunology and Infectious Diseases, University of CalgaryDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryDepartment of Microbiology, Immunology and Infectious Diseases, University of CalgaryAbstract Porphyromonas asaccharolytica and Porphyromonas uenonis are common inhabitants of the vaginal microbiome, but their presence has been linked to adverse health outcomes for women, including bacterial vaginosis and preterm birth. However, little is known about the pathogenesis mechanisms of these bacteria. The related oral opportunistic pathogen, Porphyromonas gingivalis, is comparatively well-studied and known to secrete numerous extracellular matrix-targeting proteases. Among these are the gingipain family of cysteine proteases that drive periodontal disease progression and hematogenic transmission to the placenta. In this study, we demonstrate that vaginal Porphyromonas species secrete broad-acting proteases capable of freely diffusing within the cervicovaginal niche. These proteases degrade collagens that are enriched within the cervix (type I) and chorioamniotic membranes (type IV), as well as fibrinogen, which inhibits clot formation. Bioinformatic queries confirmed the absence of gingipain orthologs and identified five serine, cysteine, and metalloprotease candidates in each species. Inhibition assays revealed that each species’ proteolytic activity can be partially attributed to a secreted metalloprotease with broad substrate specificity that is distantly related to the P. gingivalis endopeptidase PepO. This characterization of virulence activities in vaginal Porphyromonas species highlights their potential to alter the homeostasis of reproductive tissues and harm human pregnancy through clotting disruption, fetal membrane weakening, and premature cervical remodeling.https://doi.org/10.1038/s41522-022-00270-7 |
| spellingShingle | Karen V. Lithgow Vienna C. H. Buchholz Emily Ku Shaelen Konschuh Ana D’Aubeterre Laura K. Sycuro Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche npj Biofilms and Microbiomes |
| title | Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche |
| title_full | Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche |
| title_fullStr | Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche |
| title_full_unstemmed | Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche |
| title_short | Protease activities of vaginal Porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche |
| title_sort | protease activities of vaginal porphyromonas species disrupt coagulation and extracellular matrix in the cervicovaginal niche |
| url | https://doi.org/10.1038/s41522-022-00270-7 |
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