Tiling Array Based Genomic Comparisons In Streptococcus Suis

Streptococcus suis is an important zoonotic pathogen that can cause meningitis and sepsis in both pigs and humans. Some S. suis strains are more pathogenic than others. Based on differences in the presence of known or putative virulence factors, the epidemiology of infections and animal model studies. S. suis isolates have been categorized into groups with different levels of pathogenicity:intermediate pathogenic strains, highly pathogenic strains and epidemic strains. At the same time, strains which have caused severe outbreaks or sporadic invasive human infections are well recognized as highly pathogenic. Multi-locus sequence typing (MLST) has classified S. suis into more than 181 sequence types (STS). with sequence type (ST) ST1 clonal complex strains having a higher degree of virulence than other STs. Specifically, ST7 (serotype 2) of ST1 clonal complex caused two large outbreaks in China in 1998 and 2005 respectively. However, the genetic basis of the differences in pathogenicity for S. suis is still poorly understood. In this study, we analyzed 31 isolates from 23 serotypes and 25 STs by NimbleGen tiling microarray using the genome of a high pathogenicity (HP) ST1 strain, GZ1,as reference and a new algorithm to detect gene content difference. The number of genes absent in a strain ranged from 49 to 225 with a total of 632 genes absent in at least one strain, while 1346 genes were found to be invariably present in all strains as the core genome of S. suis, accounting for 68% of the GZ1 genome. The majority of genes are located in chromosomal blocks with two or more contiguous genes. Sixty two blocks are absent in two or more strains and defined as regions of difference (RDs), among which 26 are putative genomic islands (GIs). Clustering and statistical analyses revealed that 8 RDs including 6 putative GIs and 21 genes within these RDs are significantly associated with HP. Three RDs encode known virulence related factors including the extracellular factor, the capsular polysaccharide and a SrtF pilus. The strains were divided into 5 groups based on population genetic analysis of multi-locus sequence typing data and the distribution of the RDs among the groups revealed gain and loss of RDs in different groups. Our study elucidated the genomic content diversity of S. suis. identified novel genes that are significantly correlated with and potentially promote HP. These findings provide a significant insight into the evolution of pathogenicity of S. suis.