On the discovery and biological characterization of porcine β-Defensin 5 (pBD-5)

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.

Name thesis:degree_name

Doctor of Philosophy (Ph.D.)

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Large Animal Clinical Sciences

Grantor

University of Saskatchewan

Year dc:date.issued

2025

Author dc:creator

• Nery Finatto, Arthur

Advisor dc:contributor.advisor

• de Oliveira Costa, Matheus

Committee members dc:contributor.committeemember

• Gomis, Susantha
• Harding, John
• Jelinski, Murray
• Ellis, John
• Diamond, Gill

• Immunomodulation
• Antimicrobial
• Microbiome
• Antimicrobial resistance
• Host defense peptides

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10388/17032

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/17032