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Streptococcus suis 2 Transcriptional Regulator TstS Stimulates Cytokine Production and Bacteremia to Promote Streptococcal Toxic Shock-Like Syndrome.

ABSTRACT: Two large-scale outbreaks of streptococcal toxic shock-like syndrome (STSLS) have revealed Streptococcus suis 2 to be a severe and evolving human pathogen. We investigated the mechanism by which S. suis 2 causes STSLS. The transcript abundance of the transcriptional regulator gene tstS was found to be upregulated during experimental infection. Compared with the wild-type 05ZY strain, a tstS deletion mutant (?tstS) elicited reduced cytokine secretion in macrophages. In a murine infection model, tstS deletion resulted in decreased virulence and bacterial load, and affected cytokine production. Moreover, TstS expression in the P1/7 strain of S. suis led to the induction of STSLS in the infected mice. This is noteworthy because, although it is virulent, the P1/7 strain does not normally induce STSLS. Through a microarray-based comparative transcriptomics analysis, we found that TstS regulates multiple metabolism-related genes and several virulence-related genes associated with immune evasion.

SUBMITTER: Xu Z

PROVIDER: S-EPMC6020791 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Streptococcus suis 2 Transcriptional Regulator TstS Stimulates Cytokine Production and Bacteremia to Promote Streptococcal Toxic Shock-Like Syndrome.

Xu Zhongmin Z Chen Bo B Zhang Qiang Q Liu Liang L Zhang Anding A Yang Yujie Y Huang Kaisong K Huang Kaisong K Yan Shuxian S Yu Junping J Sun Xiaomei X Jin Meilin M

Frontiers in microbiology 20180619

Two large-scale outbreaks of streptococcal toxic shock-like syndrome (STSLS) have revealed Streptococcus suis 2 to be a severe and evolving human pathogen. We investigated the mechanism by which S. suis 2 causes STSLS. The transcript abundance of the transcriptional regulator gene tstS was found to be upregulated during experimental infection. Compared with the wild-type 05ZY strain, a tstS deletion mutant (ΔtstS) elicited reduced cytokine secretion in macropha ...[more]

PMID: 29973920

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Project description:BackgroundStreptococcus suis serotype 2 (S. suis 2, SS2) is a major zoonotic pathogen that causes only sporadic cases of meningitis and sepsis in humans. Most if not all cases of Streptococcal toxic shock syndrome (STSS) that have been well-documented to date were associated with the non-SS2 group A streptococcus (GAS). However, a recent large-scale outbreak of SS2 in Sichuan Province, China, appeared to be caused by more invasive deep-tissue infection with STSS, characterized by acute high fever, vascular collapse, hypotension, shock, and multiple organ failure.Methods and findingsWe investigated this outbreak of SS2 infections in both human and pigs, which took place from July to August, 2005, through clinical observation and laboratory experiments. Clinical and pathological characterization of the human patients revealed the hallmarks of typical STSS, which to date had only been associated with GAS infection. Retrospectively, we found that this outbreak was very similar to an earlier outbreak in Jiangsu Province, China, in 1998. We isolated and analyzed 37 bacterial strains from human specimens and eight from pig specimens of the recent outbreak, as well as three human isolates and two pig isolates from the 1998 outbreak we had kept in our laboratory. The bacterial isolates were examined using light microscopy observation, pig infection experiments, multiplex-PCR assay, as well as restriction fragment length polymorphisms (RFLP) and multiple sequence alignment analyses. Multiple lines of evidence confirmed that highly virulent strains of SS2 were the causative agents of both outbreaks.ConclusionsWe report, to our knowledge for the first time, two outbreaks of STSS caused by SS2, a non-GAS streptococcus. The 2005 outbreak was associated with 38 deaths out of 204 documented human cases; the 1998 outbreak with 14 deaths out of 25 reported human cases. Most of the fatal cases were characterized by STSS; some of them by meningitis or severe septicemia. The molecular mechanisms underlying these human STSS outbreaks in human beings remain unclear and an objective for further study.

Project description:Zinc is an essential trace element for all living organisms and plays pivotal roles in various cellular processes. However, an excess of zinc is extremely deleterious to cells. Bacteria have evolved complex machineries (such as efflux/influx systems) to control the concentration at levels appropriate for the maintenance of zinc homeostasis in cells and adaptation to the environment. The Zur (zinc uptake regulator) protein is one of these functional members involved in the precise control of zinc homeostasis. Here we identified a zur homologue designated 310 from Streptococcus suis serotype 2, strain 05ZYH33, a highly invasive isolate causing streptococcal toxic shock syndrome. Biochemical analysis revealed that the protein product of gene 310 exists as a dimer form and carries zinc ions. An isogenic gene replacement mutant of gene 310, the Delta310 mutant, was obtained by homologous recombination. Physiological tests demonstrated that the Delta310 mutant is specifically sensitive to Zn(2+), while functional complementation of the Delta310 mutant can restore its duration capability, suggesting that 310 is a functional member of the Zur family. Two-dimensional electrophoresis indicated that nine proteins in the Delta310 mutant are overexpressed in comparison with those in the wild type. DNA microarray analyses suggested that 121 genes in the Delta310 mutant are affected, of which 72 genes are upregulated and 49 are downregulated. The transcriptome of S. suis serotype 2 with high Zn(2+) concentrations also showed 117 differentially expressed genes, with 71 upregulated and 46 downregulated. Surprisingly, more than 70% of the genes differentially expressed in the Delta310 mutant were the same as those in S. suis serotype 2 that were differentially expressed in response to high Zn(2+) concentration, consistent with the notion that 310 is involved in zinc homeostasis. We thus report for the first time a novel zinc-responsive regulator, Zur, from Streptococcus suis serotype 2.

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Streptococcus suis 2 Transcriptional Regulator TstS Stimulates Cytokine Production and Bacteremia to Promote Streptococcal Toxic Shock-Like Syndrome.

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<i>Streptococcus suis</i> 2 Transcriptional Regulator TstS Stimulates Cytokine Production and Bacteremia to Promote Streptococcal Toxic Shock-Like Syndrome.

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