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

Chen Chen,George F Gao,Changjun Wang,Yongqiang Jiang,Zhaobiao Guo,Jinghua Yan,Wen Sun,Youjun Feng,Ruifu Yang,Xinxing Zhu,Jian Wang,Xiaoning Wang,Yajun Song,Jun Wang,Huanming Yang,Ming Li,Wei Dong,Xiuzhen Pan,Haibo Sun,Yaqing Dong,Di Liu,Jiaqi Tang,Jing Wang,Junchao Ge,Tao Feng,Jun Yu,Zijian Feng ,Ai-Ping Ju

doi:10.1371/journal.pone.0000315

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.

Highlights

Streptococcus suis (S. suis) infection is notorious for causing serious zoonotic diseases manifesting as meningitis, septicaemia, arthritis, etc. in addition to its great economic impact on swine industries worldwide each year[1,2]
Further analysis of 89K showed clearly that it satisfies most the criteria to be considered as a pathogenicity island (PAI) (Fig. 3): 1) In view of virulence-associated factor (VAF), we identified a zeta-toxin, three ABC transporter cassettes that play important roles in controlling efflux and influx across cell membranes for small substances, two transduction system (TCS) with key links to quorum sensing to initiate the infection cycle through regulating efficient bacterial density and adapting to different environments, and three different components of T4SS; 2) 89K, a candidate PAI is present in the two highly virulent strains, 98HAH12 and
Combined with the above comparative genomic results derived from 4 strains of suis serotype 2 (SS2) (98HAH12, 05ZYH33, P1/7 and 05HAS68), our results demonstrate clearly that 89K is a novel mosaic PAI candidate and is prevalent and unique to the Chinese SS2 virulent strains responsible for the two severe outbreaks with a hallmark of streptococcal toxic shock syndrome (STSS) in 1998 and 2005

Summary

Introduction

Streptococcus suis (S. suis) infection is notorious for causing serious zoonotic diseases manifesting as meningitis, septicaemia, arthritis, etc. in addition to its great economic impact on swine industries worldwide each year[1,2]. 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. 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. Our finding 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

Methods

Results

Conclusion