{"id":{"repo_id":"sask","oai_identifier":"oai:harvest.usask.ca:10388/17032"},"canonical_url":"https://search.dev.ndltd.org/etd/sask/oai:harvest.usask.ca:10388/17032","repository":{"repo_id":"sask","name":"University of Saskatchewan","base_url":"https://harvest.usask.ca/server/oai/request"},"display":{"title":"On the discovery and biological characterization of porcine β-Defensin 5 (pBD-5)","abstract":"Feeding an ever-growing population, antimicrobial resistance (AMR) and infection control are among the biggest challenges humanity faces in the XXI century. Host defense peptides (HDPs), such as porcine β-defensins (pBDs), have gained attention for their immunomodulatory, microbiome-modulating, and antimicrobial properties. This thesis describes the discovery, synthesis, and biological characterization of a novel porcine β-defensin, pBD-5, and its role in disease resilience, immune modulation, and microbiome interactions. To elucidate the biological significance of pBD-5, we employed a multifaceted approach, integrating genomic analysis, in vitro assays, and in vivo models. We identified the genomic region encoding pBD-5 in pigs and investigated its role in the host response to Brachyspira hyodysenteriae. Functional assays revealed that pBD-5 modulates key immune pathways, downregulating inflammatory mediators such as IL-17, toll-like and NOD-like receptors. We synthesized pBD-5 using an orthogonal chemical approach to assess its structural and functional properties. The oxidized form, with correctly folded disulfide bonds, exhibited antimicrobial activity against Escherichia coli and Staphylococcus epidermidis at physiologically relevant concentrations, underscoring the importance of oxidative folding for its bioactivity. Notably, pBD-5 selectively enhanced mitochondrial activity in B-cells, indicating a novel immunomodulatory function that could influence adaptive immunity. In an in vivo mouse model, oral administration of pBD-5 modulated the gut microbiome, notably reducing Prevotella spp. abundance and increasing microbial diversity. These results suggest that pBD-5 functions as a key component of the porcine innate immune system, with broader applications potentially leading into adaptive immunity. The findings presented in this thesis contribute to the understanding of HDPs with immunomodulatory and microbiome-modulating properties, with a particular focus on pBD-5. By bridging fundamental research with practical applications, this work provides valuable insights into harnessing pBD-5 as a biotechnological tool for mitigating AMR and enhancing animal health. Future studies should focus on validating its therapeutic potential in swine models and exploring combinatory approaches with other HDPs or probiotics for optimized disease control strategies.","abstract_html":"Feeding an ever-growing population, antimicrobial resistance (AMR) and infection control are among the biggest challenges humanity faces in the XXI century. Host defense peptides (HDPs), such as porcine β-defensins (pBDs), have gained attention for their immunomodulatory, microbiome-modulating, and antimicrobial properties. This thesis describes the discovery, synthesis, and biological characterization of a novel porcine β-defensin, pBD-5, and its role in disease resilience, immune modulation, and microbiome interactions. To elucidate the biological significance of pBD-5, we employed a multifaceted approach, integrating genomic analysis, in vitro assays, and in vivo models. We identified the genomic region encoding pBD-5 in pigs and investigated its role in the host response to Brachyspira hyodysenteriae. Functional assays revealed that pBD-5 modulates key immune pathways, downregulating inflammatory mediators such as IL-17, toll-like and NOD-like receptors. We synthesized pBD-5 using an orthogonal chemical approach to assess its structural and functional properties. The oxidized form, with correctly folded disulfide bonds, exhibited antimicrobial activity against Escherichia coli and Staphylococcus epidermidis at physiologically relevant concentrations, underscoring the importance of oxidative folding for its bioactivity. Notably, pBD-5 selectively enhanced mitochondrial activity in B-cells, indicating a novel immunomodulatory function that could influence adaptive immunity. In an in vivo mouse model, oral administration of pBD-5 modulated the gut microbiome, notably reducing Prevotella spp. abundance and increasing microbial diversity. These results suggest that pBD-5 functions as a key component of the porcine innate immune system, with broader applications potentially leading into adaptive immunity. The findings presented in this thesis contribute to the understanding of HDPs with immunomodulatory and microbiome-modulating properties, with a particular focus on pBD-5. By bridging fundamental research with practical applications, this work provides valuable insights into harnessing pBD-5 as a biotechnological tool for mitigating AMR and enhancing animal health. Future studies should focus on validating its therapeutic potential in swine models and exploring combinatory approaches with other HDPs or probiotics for optimized disease control strategies.","abstract_has_math":false,"creators":["Nery Finatto, Arthur"],"institution":"University of Saskatchewan","degree_name":"Doctor of Philosophy (Ph.D.)","degree_level":"Doctoral","degree_discipline":"Large Animal Clinical Sciences","degree_department":null,"school":null,"contributors":[],"advisors":["de Oliveira Costa, Matheus"],"committee_chairs":[],"committee_members":["Gomis, Susantha","Harding, John","Jelinski, Murray","Ellis, John","Diamond, Gill"],"year":2025,"date_issued":"2025-06-24","date_published":"2025-06-24","updated_at":"2026-07-24T04:26:54Z","subjects":["Immunomodulation","Antimicrobial","Microbiome","Antimicrobial resistance","Host defense peptides"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10388/17032","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["de Oliveira Costa, Matheus"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Gomis, Susantha","Harding, John","Jelinski, Murray","Ellis, John","Diamond, Gill"]},{"key":"dc:creator","label":"Author","values":["Nery Finatto, Arthur"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-06-24T16:35:30Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-06-24"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Large Animal Clinical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (Ph.D.)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Saskatchewan"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Immunomodulation","Antimicrobial","Microbiome","Antimicrobial resistance","Host defense peptides"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10388/17032"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Feeding an ever-growing population, antimicrobial resistance (AMR) and infection control are among the biggest challenges humanity faces in the XXI century. Host defense peptides (HDPs), such as porcine β-defensins (pBDs), have gained attention for their immunomodulatory, microbiome-modulating, and antimicrobial properties. This thesis describes the discovery, synthesis, and biological characterization of a novel porcine β-defensin, pBD-5, and its role in disease resilience, immune modulation, and microbiome interactions. To elucidate the biological significance of pBD-5, we employed a multifaceted approach, integrating genomic analysis, in vitro assays, and in vivo models. We identified the genomic region encoding pBD-5 in pigs and investigated its role in the host response to Brachyspira hyodysenteriae. Functional assays revealed that pBD-5 modulates key immune pathways, downregulating inflammatory mediators such as IL-17, toll-like and NOD-like receptors. We synthesized pBD-5 using an orthogonal chemical approach to assess its structural and functional properties. The oxidized form, with correctly folded disulfide bonds, exhibited antimicrobial activity against Escherichia coli and Staphylococcus epidermidis at physiologically relevant concentrations, underscoring the importance of oxidative folding for its bioactivity. Notably, pBD-5 selectively enhanced mitochondrial activity in B-cells, indicating a novel immunomodulatory function that could influence adaptive immunity. In an in vivo mouse model, oral administration of pBD-5 modulated the gut microbiome, notably reducing Prevotella spp. abundance and increasing microbial diversity. These results suggest that pBD-5 functions as a key component of the porcine innate immune system, with broader applications potentially leading into adaptive immunity. The findings presented in this thesis contribute to the understanding of HDPs with immunomodulatory and microbiome-modulating properties, with a particular focus on pBD-5. By bridging fundamental research with practical applications, this work provides valuable insights into harnessing pBD-5 as a biotechnological tool for mitigating AMR and enhancing animal health. Future studies should focus on validating its therapeutic potential in swine models and exploring combinatory approaches with other HDPs or probiotics for optimized disease control strategies."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["On the discovery and biological characterization of porcine β-Defensin 5 (pBD-5)"]}]}],"canonical_facts":{"dc:contributor.advisor":["de Oliveira Costa, Matheus"],"dc:contributor.committeemember":["Gomis, Susantha","Harding, John","Jelinski, Murray","Ellis, John","Diamond, Gill"],"dc:creator":["Nery Finatto, Arthur"],"dc:date.accessioned":["2025-06-24T16:35:30Z"],"dc:date.issued":["2025-06-24"],"dc:description.abstract":["Feeding an ever-growing population, antimicrobial resistance (AMR) and infection control are among the biggest challenges humanity faces in the XXI century. Host defense peptides (HDPs), such as porcine β-defensins (pBDs), have gained attention for their immunomodulatory, microbiome-modulating, and antimicrobial properties. This thesis describes the discovery, synthesis, and biological characterization of a novel porcine β-defensin, pBD-5, and its role in disease resilience, immune modulation, and microbiome interactions. To elucidate the biological significance of pBD-5, we employed a multifaceted approach, integrating genomic analysis, in vitro assays, and in vivo models. We identified the genomic region encoding pBD-5 in pigs and investigated its role in the host response to Brachyspira hyodysenteriae. Functional assays revealed that pBD-5 modulates key immune pathways, downregulating inflammatory mediators such as IL-17, toll-like and NOD-like receptors. We synthesized pBD-5 using an orthogonal chemical approach to assess its structural and functional properties. The oxidized form, with correctly folded disulfide bonds, exhibited antimicrobial activity against Escherichia coli and Staphylococcus epidermidis at physiologically relevant concentrations, underscoring the importance of oxidative folding for its bioactivity. Notably, pBD-5 selectively enhanced mitochondrial activity in B-cells, indicating a novel immunomodulatory function that could influence adaptive immunity. In an in vivo mouse model, oral administration of pBD-5 modulated the gut microbiome, notably reducing Prevotella spp. abundance and increasing microbial diversity. These results suggest that pBD-5 functions as a key component of the porcine innate immune system, with broader applications potentially leading into adaptive immunity. The findings presented in this thesis contribute to the understanding of HDPs with immunomodulatory and microbiome-modulating properties, with a particular focus on pBD-5. By bridging fundamental research with practical applications, this work provides valuable insights into harnessing pBD-5 as a biotechnological tool for mitigating AMR and enhancing animal health. Future studies should focus on validating its therapeutic potential in swine models and exploring combinatory approaches with other HDPs or probiotics for optimized disease control strategies."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/10388/17032"],"dc:language.iso":["en"],"dc:subject":["Immunomodulation","Antimicrobial","Microbiome","Antimicrobial resistance","Host defense peptides"],"dc:title":["On the discovery and biological characterization of porcine β-Defensin 5 (pBD-5)"],"dc:type":["Thesis"],"thesis:degree_discipline":["Large Animal Clinical Sciences"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Doctor of Philosophy (Ph.D.)"],"thesis:institution_name":["University of Saskatchewan"]},"updated_at":"2026-07-24T04:26:54Z"}