The Deficiency Of Sia-capped Capsule Effects The Interactions Between Streptococcus Suis Serotype2and The Hosts

Streptococcus suis is an emerging zoonotic pathogen responsible for a wide rangeof life-threatening diseases in pigs and human. To date, thirty-three serotypes (types1/2,1-31and33) of S.suis have been described, of which Streptococcus suisserotype2(S.suis2) is the most frequently isolated and associated with disease.Furthermore, two emerging outbreaks of S.suis2in China (one is in JiangsuProvince,1998, and the other one is in Sichuan Province,2005) raised considerableinternational concerns among the public health professionals. A key feature of thesetwo outbreaks is the prevalence of streptococcal toxic shock syndrome (STSS)manifesting itself as acute high fever, multiple organ failures, short course of diseaseand high lethality.The CPS, which is the necessary components of the high pathogenicity of S.suis,is thus far the only proven critical virulence factor. Sialic acid, one compotents ofcapsular polysaccharide, has been confirmed as a virulence factor for streptococcuscausing meningitis. For example, sialic acid is considered as an important virulencefactor in the B Group of Streptococcus pneumoniae, it plays an important role for thebacteria to break through the blood brain barrier. But the influence of sia-cappedcapsule for the pathogenicity of S.suis2is poorly understood. In this research, thehigh pathogenic strain05ZYH33strain, the mutations Δcps2B and ΔneuB, thecorresponding complementary strains cΔcps2B and cΔneuB are studied, and theexperimental contents and the results mainly include the following aspects:1. The research of biological characteristics: In order to further explain the role ofsia-capped polysaccharide in the pathogenicity of05ZYH33, the distributions of cps2B and neuB in different serotypes of S.suis and biological characters ofexperimental strains were studied. We found that cps2B and neuB mainly distributedin S.suis2and some isolates of the pathogenic serotypes (1/2,1,14,19); Comparedwith the wild type strain, the microstructure of the mutants had a significant change.The capsule of ΔneuB was obviously thinner, and that of Δcps2B was absent; thecontent of saliva acid was significantly decreased in ΔneuB and Δcps2B.2. The sia-capped capsule of S.suis2influences virulence and host inflammatoryresponses: To study the interactions between S.suis2and the host, the differences ofthe pathogenicity of the experimental strains were compared in the mice model. Theexperiment showed that the virulence of mutants was significantly reduced, andwhen the genes were restored, toxicity levels were returned to that of the wild typestrain; the quantities of the wild type strain and the mutants distributed in blood hadsignificant difference. Compared with the mutants, the ability of infected mice toeliminate the wild type strain was weaker. In mice experiments, we found that thewild type strain can cause different degrees of brain damage, and the significanthyperplasia of glial cell, scattered bleeding and the infiltration of leukocyte weredetermined; In vitro tests, the mutants can stimulate the whole blood cells to secretehigher levels of MCP-1and IL-6, prompting the inhibition effect of sialylation ofcapsular polysaccharide in the hosts’ recognition and response.3. The interactions between S.suis2and the host cells: Further we studied theinteractions between S.suis2and the host cells. On the one hand, the ability ofadhesion to and invasion of the human epithelial cells (Hep-2) and endothelial cells(HBMEC) was compared; On the other hand, the survival ability of the wild typestrain and mutants were studied after interacted with the human mononuclear cells(Human THP-1monocytes, THP-1), and the levels of cytokine secreted by THP-1for the stimulation of the experimental strains were detected. The experimental results showed that the abilities of the mutants to adhere to and invade of the cellswere increased, and for the absence of sialylation of capsular polysaccharide, themutants’ ability to escape the damage of the immune cells was decreased.To sum up, this study confirmed that cps2B and neuB played a key role insynthesis of capsular polysaccharide. Sia-capped capsule was an important virulencefactor of S.suis2, and we preliminarily illuminated the role of it in the aspects ofbacterial adhesion and planting, invasion, spread. It lays a foundation for the futurestudy about how to participate in the pathogenic process of sialylation of capsularpolysaccharide of S.suis2and the molecular mechanism of S.suis2to against thedefense of the host innate immunity.