Investigating the link between genome reduction and pathogenicity using an emerging zoonotic pathogen. (360G-Wellcome-109385_Z_15_Z)

Bacterial pathogens very often have smaller genomes and fewer genes than their nearest non-pathogenic relatives. This pattern applies in phyla as diverse as the Firmicutes, Tenericutes and Proteobacteria. However, despite much speculation, it remains unclear why this pattern holds. I will address this question using Streptococcus suis, a bacterium that is common in non-pathogenic forms, but which also causes serious diseases in pigs and humans. My preliminary data show that S. suis has made seve ral recent and independent transitions to pathogenicity, each associated with genome reduction, and that the gene loss is non-random, suggesting that the process might be predictable. I propose to sample whole genomes of global S. suis populations. Then, I will carry out the first large-scale tests of the various hypotheses linking genome reduction and pathogenicity. This will require functional data, and new statistical approaches. Next, I will use methods from Bayesian phylogeography to place the genome reduction events in their epidemiological context, identifying factors that lead predictably to increased virulence. Finally, I will use genome reduction as a tool to uncover new virulence genes. Together, the proposed research will further our understanding of an important emerging pathogen, and of pathogenicity much more broadly.