Background: Streptococcus suis is a zoonotic pathogen that infects pigs and can occasionally cause serious infections in
humans. S. suis infections occur sporadically in human Europe and North America, but a recent major outbreak has been
described in China with high levels of mortality. The mechanisms of S. suis pathogenesis in humans and pigs are poorly
understood.
Methodology/Principal Findings: The sequencing of whole genomes of S. suis isolates provides opportunities to
investigate the genetic basis of infection. Here we describe whole genome sequences of three S. suis strains from the same
lineage: one from European pigs, and two from human cases from China and Vietnam. Comparative genomic analysis was
used to investigate the variability of these strains. S. suis is phylogenetically distinct from other Streptococcus species for
which genome sequences are currently available. Accordingly, ,40% of the ,2 Mb genome is unique in comparison to
other Streptococcus species. Finer genomic comparisons within the species showed a high level of sequence conservation;
virtually all of the genome is common to the S. suis strains. The only exceptions are three ,90 kb regions, present in the two
isolates from humans, composed of integrative conjugative elements and transposons. Carried in these regions are coding
sequences associated with drug resistance. In addition, small-scale sequence variation has generated pseudogenes in
putative virulence and colonization factors.
Conclusions/Significance: The genomic inventories of genetically related S. suis strains, isolated from distinct hosts and
diseases, exhibit high levels of conservation. However, the genomes provide evidence that horizontal gene transfer has
contributed to the evolution of drug resistance.