Characterization of emerging Brachyspira pathogens in swine: Applications to disease control

Abstract

Swine dysentery (SD) is a mucohemorrhagic diarrheal disease of pigs and is a welfare and economic issue globally. Its re-emergence in the U.S. after two decades of quiescence was associated not only with B. hyodysenteriae but also with a novel spirochete, Brachyspira hampsonii. The overall objective of this dissertation was to determine the genotypic, antimicrobial susceptibility and virulence factors of these pathogens in order to understand the re-emergence of SD in the U.S. As the re-emergent isolates were genetically related to historic isolates, it is likely that B. hyodysenteriae persisted in the U.S. over the last two decades without causing overt clinical disease. B. hampsonii isolates from migratory birds and pigs were found to be closely related, thus highlighting the potential role of migratory birds in its emergence in swine herds. When the broth microdilution method was compared with the agar dilution/strip test methods for antimicrobial susceptibility testing (AST) of various Brachyspira species, with the exception of carbadox, all other evaluated antimicrobials (tiamulin, valnemulin, lincomycin, tylosin and doxycycline) showed high agreement between the methods. Most Brachyspira isolates demonstrated high susceptibility to tiamulin, valnemulin and carbadox, heterogeneous susceptibility to doxycycline and low susceptibility to lincomycin and tylosin. Decreased tiamulin susceptibility, when rarely identified, was associated with the genotype, stage of production and production system from which the isolate originated, possibly reflecting local antimicrobial usage. Overall, antimicrobial resistance did not seem likely to be the cause of the re-emergence of SD in the U.S. The genomic comparison of U.S. B. hyodysenteriae field isolates revealed several mobile elements that showed variation between the isolates and are likely associated with the evolution of this species. Genes involved in carbohydrate and cell wall biosynthesis, cell survival and host-pathogen interaction were predicted to be potentially associated with B. hyodysenteriae virulence. Based on a comprehensive polyphasic approach (multiple whole-genome comparison, genotypic and phenotypic data), Brachyspira hampsonii sp. nov. was classified as a unique species with genetically diverse yet phenotypically similar ‘genomovars’. Finally, this work also provided information that can directly (genotyping, ASTs) and indirectly (gene candidates for diagnostic tests and vaccines) be applied to disease control.