Molecular characterisation of antimicrobial resistance in Brachyspira hyodysenteriae, aetiological agent for swine dysentery

Brachyspira hyodysenteriae is the aetiological agent of swine dysentery, a globally distributed disease that causes profound economic loss. Although infection is generally treated with pleuromutilin or other antibiotics, reports of resistance worldwide threaten continued effective control. We undertook antibiotic susceptibility testing and whole-genome analysis of 37 Brachyspira hyodysenteriae isolates to elucidate the dynamics of pleuromutilin resistance acquisition. Genome-wide association studies identified a new pleuromutilin resistance gene, tva(A). Study of resistant mutants generated in vitro showed that tva(A) conferred reduced pleuromutilin susceptibility and facilitated the development of higher-level resistance via mutations in chromosomal genes. Furthermore tva(A) raised the mutant prevention concentration above the reported in vivo antibiotic concentrations obtained when administered at certain doses. We have identified a new marker for pleuromutilin resistance and provided evidence to inform treatment regimes, and reduce the development of resistance to this class of highly important antimicrobial agents.