Infectious diseases in pig production pose significant challenges to global food security, agricultural economics, and trade. Control and eradication efforts for these diseases rely on effective herd management strategies, biosecurity measures, antibiotic therapy, and immunization. However, the ongoing evolutionary arms race between hosts and pathogens leads to the continuous circulation, evolution, and emergence of new pathogen variants that are highly virulent, transmissible, and resistant to existing therapeutics and vaccines. Porcine reproductive and respiratory syndrome virus (e.g., PRRSV-2) and Streptococcus suis are prime examples of such pathogens, exhibiting continuous evolution and existing in both endemic and epidemic forms within global swine production systems. The genetic and antigenic variability in PRRSV-2 and the diversity, horizontal gene transfer, antimicrobial resistance (AMR), and multidrug resistance (MDR) in S. suis significantly challenge current control programs, including vaccination and antibiotic therapy, resulting in substantial financial burden for swine producers. The application of molecular and evolutionary genetic tools, combined with epidemiological approaches that consider multi-scale data (animal-, farm-, and system-levels), provides valuable insights into the complexities of these diseases, including transmission, pathogenesis, virulence, host interactions, and resistance or immune evasion mechanisms.

This study applied advanced molecular and evolutionary genetics techniques to assess the PRRSV-2 and S. suis strains circulating in swine production systems in recent years. Chapter 1 examined the genetic diversity, spatiotemporal patterns, and underlying evolutionary processes of PRRSV-2 strains circulating in two swine production systems in the Midwest United States from 2001 to 2020, using ORF5 gene sequencing. Chapter 2 assessed the genetic diversity, spatiotemporal patterns, and virulence profiles of S. suis strains isolated from North America, Latin America, and Europe between 2014 and 2024, utilizing draft genomes. Chapter 3 investigated the spatiotemporal distribution and genetic determinants of AMR and MDR of these S. suis strains, focusing on the coexistence of genes associated with virulence and resistance to antibiotics, biocides, and heavy metals, and their correlation with AMR phenotypes. Together, these three chapters offered valuable insights into key traits of PRRSV-2 and S. suis strains, including their diversity, adaptation, persistence, pathogenicity, virulence, resistance, and immune evasion. This knowledge will be instrumental in developing strategies to control the spread of infections and AMR. Potential control strategies include the development of novel therapeutics and vaccines that address pathogen diversity, evolving pathogenicity, and resistance of pathogens, as well as improving infection management through strategies like optimizing pig flow management to limit the spread of resistant and virulent strains and applying risk-based approaches at the farm level. However, integrating molecular and evolutionary genetic techniques into epidemiologic studies introduces new challenges in study design, implementation, and analysis, requiring careful consideration to ensure robust and accurate results.