Emerging bacterial pathogens threaten global health and food security, and so it is important to ask whether these transitions to pathogenicity have any common features. We present a systematic study of the claim that pathogenicity is associated with genome reduction and gene loss. We compare broad-scale patterns across all bacteria, with detailed analyses of Streptococcus suis, an emerging zoonotic pathogen of pigs, which has undergone multiple transitions between disease and carriage forms. We find that pathogenicity is consistently associated with reduced genome size across three scales of divergence (between species within genera, and between and within genetic clusters of S. suis). While genome reduction is also found in mutualist and commensal bacterial endosymbionts, genome reduction in pathogens cannot be solely attributed to the features of their ecology that they share with these species, i.e. host restriction or intracellularity. Moreover, other typical correlates of genome reduction in endosymbionts (reduced metabolic capacity, reduced GC content, and the transient expansion of non-functional elements) are not consistently observed in pathogens. Together, our results indicate that genome reduction is a predictive marker of pathogenicity in bacteria.

For each genus containing at least one pathogen and one non-pathogen, we downloaded all available complete genomes (see Table S2). (Draft genomes were excluded because we observed that they varied substantially in length for a few species.) We then used Phylosift (Darling et al. 2014) to align 37 single copy orthologs identified as universal to all bacteria. Concatenated alignments of these loci were checked and corrected by eye.