Complex Population Structure and Virulence Differences among Serotype 2 Streptococcus suis Strains Belonging to Sequence Type 28

Abstract

Streptococcus suis is a major swine pathogen and a zoonotic agent. Serotype 2 strains are the most frequently associated with disease. However, not all serotype 2 lineages are considered virulent. Indeed, sequence type (ST) 28 serotype 2 S. suis strains have been described as a homogeneous group of low virulence. However, ST28 strains are often isolated from diseased swine in some countries, and at least four human ST28 cases have been reported. Here, we used whole-genome sequencing and animal infection models to test the hypothesis that the ST28 lineage comprises strains of different genetic backgrounds and different virulence. We used 50 S. suis ST28 strains isolated in Canada, the United States and Japan from diseased pigs, and one ST28 strain from a human case isolated in Thailand. We report a complex population structure among the 51 ST28 strains. Diversity resulted from variable gene content, recombination events and numerous genome-wide polymorphisms not attributable to recombination. Phylogenetic analysis using core genome single-nucleotide polymorphisms revealed four discrete clades with strong geographic structure, and a fifth clade formed by US, Thai and Japanese strains. When tested in experimental animal models, strains from this latter clade were significantly more virulent than a Canadian ST28 reference strain, and a closely related Canadian strain. Our results highlight the limitations of MLST for both phylogenetic analysis and virulence prediction and raise concerns about the possible emergence of ST28 strains in human clinical cases.

Distribution of Suicin Gene Clusters in Streptococcus suis Serotype 2 Belonging to Sequence Types 25 and 28

“…These strains were isolated from diseased pigs in Canada, the United States, Japan, and Thailand and have been described previously [12, 13]. …”

“…The genomes of the 102 strains were sequenced as paired-end reads with either a HiSeq 2500 or a MiSeq instrument (Illumina, San Diego, CA, USA) as described in previous reports [12, 13]. Sequences with accession numbers SRP065686 and SRP058193, for ST25 and ST28 strains, respectively, were retrieved from the NCBI sequence read archive (SRA).…”

Tools for Molecular Epidemiology of Streptococcus suis

“…WGS approaches have increasingly been used to investigate S. suis isolates, including molecular determination of serotype [44], characterization of outbreaks [45,46], evaluation of S. suis reinfection [47], and to determine the population structure of S. suis isolates of serotype 2 belonging to ST25 and ST28 [48,49], as well as of serotype 9 [50]. WGS-based bacterial typing strategies commonly use one of two approaches: SNP (sequence)-based, or MLST (allele)-based.…”

Chromosomal Conjugative and Mobilizable Elements in Streptococcus suis: Major Actors in the Spreading of Antimicrobial Resistance and Bacteriocin Synthesis Genes

“…Bacterial genomes analyzed in this work were sequenced previously [11,40,45]. DNA sequencing short-reads (see accession numbers listed in Table S1) were retrieved from the Sequence Read Archive of NCBI (https://www.ncbi.nlm.nih.gov/sra).…”