Estrada, April2021-10-132021-10-132021-08https://hdl.handle.net/11299/225025University of Minnesota Ph.D. dissertation. 2021. Major: Veterinary Medicine. Advisors: Connie Gebhart, Douglas Marthaler. 1 computer file (PDF); x, 154 pages + 5 supplementary file.Streptococcus suis is a significant cause of systemic and central nervous system (CNS) disease in pigs and is a welfare and economic issue worldwide. The control of S. suis disease in the United States is hindered by the lack of contemporary genotypic and epidemiological data. Lacking is information on the genomic differences between pathogenic or disease-causing strains and commensal strains. The overall goal of this dissertation was to investigate the distribution and population structure of S. suis and determine the genomic characteristics and virulence-associated factors of pathogenic strains to better understand the observed persistence and severity of S. suis infections in the United States. Serotyping and multilocus sequence type (MLST) are traditional methods for characterizing S. suis. U.S. isolates represented uniquely prevalent subtypes with several subtypes being associated with disease as determined by pathotype classifications. These results increased the knowledge about the serotype distribution and population structure of S. suis in the United States and established a link between subtype and pathotype to better predict pathogenicity. Genomic prediction of previously published virulence-associated genes (VAGs) of S. suis illustrated a high number of VAGs found across pathotypes indicating pathogenic and commensal strains share many VAGs. Statistical analysis of VAGs and pathotype classifications confirmed classical virulence markers of Eurasian strains are not sufficient for identifying pathogenic strains in the U.S. Regression analysis was used to predict the association of published VAGs of S. suis and pathotype. Results indicated that VAG profiling should be complemented with the two newly proposed VAGs. This supports previous studies that North American and Eurasian pathogenic strains are genetically different. The same MLST-VA genotype patterns were identified in multiple production companies, suggesting these patterns may be widespread as opposed to originating from a common source. Comparative pan-genome analysis of S. suis isolates illustrated genomic regions (accessory genome) associated with virulence-related functions. Further analysis of the accessory genome by pathotype revealed three novel candidate VAGs of S. suis with potential virulence-related functions that may better serve as predictive markers of pathogenicity. Based on in silico analysis, high resistance to tetracyclines and erythromycin were observed regardless of pathotype, and mobile genetic elements appeared to play a limited role in the transfer of antimicrobial resistance genes in S. suis. In summary, this dissertation investigated the genomic diversity of S. suis, the subtyping of pathogenic and commensal strains, and the identification and potential epidemiological surveillance of clones within and between swine production companies. The information provided by our work can be applied to diagnostics, epidemiological monitoring, and control of S. suis. Supplementary information:Additional file 4.1. Gene clusters (n=8,231) identified in Roary analysis of S. suis genomes (n=208). Binary matrix representing the presence (1) and absence (0) of all 8,231 gene clusters identified by the Roary analysis performed on all 208 S. suis genomes. [.xlsx] Additional file 4.2. COG functional classifications for the 995 pan-gene clusters that met the criteria. Results of the BLAST searches against the Predicted Cluster of Orthologous Groups (COG) database. Classification as core or accessory and present (yes) or absent (no) in each pathotype is listed. [.xlsx] Additional file 4.3. Gene clusters (n=6,407) identified in Roary analysis of S. suis genomes (n=161). Binary matrix representing the presence (1) and absence (0) of all 6,407 gene clusters identified by the Roary analysis performed on the 161 S. suis genomes representing only the pathogenic and commensal pathotypes. [.xlsx] Additional file 4.4. ARGs, VAGs, and MGEs identified in S. suis genomes (n=208). Binary matrix representing the presence (1/yes) and absence (0/no) of ARGs, MGEs, MGE-associated ARGs, and MGE-associated VAGs. [.xlsx] Additional file 4.5. Prokka annotations of MGE drafts. List of prokka annotations of the plasmid, ICE, IME, composite transposon, and 89K PAI draft sequences identified in this study. [.xlsx]enThesis or Dissertation