A Glimpse of Streptococcal Toxic Shock Syndrome from Comparative Genomics of S. suis 2 Chinese Isolates

Abstract

Background Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood.Methods and FindingsTo elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of ∼89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence.ConclusionsTo our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections.

Two novel regulators of N‐acetyl‐galactosamine utilization pathway and distinct roles in bacterial infections

“…2006; Chen et al. 2007). We are aware that SS2 has spread to more than 30 countries/regions and claims nearly 1600 cases of human infections worldwide (Feng et al.…”

Identification of a Novel Streptococcal Adhesin P (SadP) Protein Recognizing Galactosyl-α1–4-galactose-containing Glycoconjugates

“…A recent outbreak in China was caused by type 2 strains and was associated with high mortality to humans (12). In addition to individual virulence factors, pathogenicity islands and islands for pilus biogenesis have recently been identified (13)(14)(15).…”

Predominance of Streptococcus suis ST1 and ST7 in human cases in China, and detection of a novel sequence type, ST658

“…2B). 1,11,15 This observation suggests that horizontal transfer of 89K PAI occurred from ST7 to ST658, or from ST7 to ST1, which have evolved to become ST658. Furthermore, comparison of the 89K PAI-associated region from available genomes from different countries showed that PAI regions of strains are variegated and can be grouped into 4 types according to the features and structures of the PAI-associated region (Fig.…”

“…5 Comparative analysis showed that the tetM also exists in S. suis strains from human (05ZYH33, 98HAH33 and SC84) linked to 2 outbreaks, 1,11 but is absent from the human strain GZ1 relating to sporadic infections (Table S2). 12 To predict the virulence of S. suis LSM102, its genome was screened for 15 virulence factors linked to immune evasion or systemic infection, including SalKR, NisKR, Epf, Fhb, IgA1, Ide Ssuis , MRP, Sly, Nudp, SsnA, EndA, ScpA and SsadS.…”

“…The growth curve of LSM102 is similar to P1/7 (data not shown), a highly virulent, international reference strain of S. suis. 11 To evaluate the virulence of S. suis strains, 10 6-week-old BALB/c mice (per group) were inoculated intraperitoneally with 2£10 8 colony forming units (CFU) of S. suis P1/7 or LSM102, as described previously. 13 All the animal experimental protocols were approved by the Laboratory Animal Monitoring Committee of Huazhong Agricultural University and performed accordingly.…”