Identification And Characterization Of IgA1 Protease Of Streptococcus Suis 2

Streptococcus suis type serotype2 (SS2) is one of an important zoonosis. Recently the pathogenesis of the S.suis is unknown. The reseach on Streptococcus suis 2 is mainly concentraining on virulence-related factors. It has been shown that the polysaccharide capsule is a general recognition virulence factor of the bacterium, Several other factors have been shown to be potential virulence of SS2.So discovery and identification of novel virulence-related factors are still the focal point of reseach for emploring the pathogenic mechanism of Streptococcus suis.It is well known that secretory IgA is the major effector of mucous immune system and not easy to be hydrolyzed by prolease, and there is full of SIgA in external secretion.So IgA-mediated immunity is thought to provide a first line of defense against recurrent mucosal pathogens. SIgA is the principal immunologic defense of respiratory and other mucosal surfaces in the body, and IgAl represents 90% of the IgA within the human respiratory tract. However, pathogenic microorganism including Haemophilus influenzae, Neisseria meningitidis, Streptococcus sanguis and Streptococcus pneumoniae seem to have acquired counter mechanisms by convergent evolution, which involved secretion of a protease that specifically cleaves human IgAl in its hinge region. These results in the separation of the two antigen binding Fab fragments from the Fc tail, and the Fab fragments still retain their capacity to bind to bacterial surface antigens,while the Fc tail without Fab fragments is inactived.Therefore, IgAl protease-producing bacteria may take advantage of released Fab fragments by enhancing the surface hydrophobicity and thus adhesion and by blocking the access of intact antibodies. IgAl protease is one of important virulence-related factor of these pathogenion.Analysis of the deduced amino acid sequence of the 05ZYH33 gene from SS2 revealed that HP1022 shared similar primary structure to the IgA1 protease. The recombinant HP1022 was able to cleave human IgA1, and it resulted in the separation of the two antigen binding Fab fragments from the Fc tail.And the recombinant protein was expressed in vivo, which was confirmed by the finding that the protein showed good immunoreactivity to convalescent sera. Furtherly analysising, a gene mutant strain Aiga of SS2 was hereditarily stable.And there were not significant diference of Growth curve and biochemical effect between WT strain and the mutant. However, the deletion of iga could contribute to the less ability to adhere to the Hep-2 cells, and it also lower the ability of S. suis to resist neutrophils killing. In addition, the Aiga mutant showed lower virulence than WT in both the murine and porcine models of infection. And the gene existed in most pathogenic strains but scarcely in non-invasive isolates by PCR, The present study strongly suggested that IgA1-protease is high related to the pathogenesis of S. suis, which indicated that one of virulence-related factor of SS2.Discovery of novel virulence-related factors could provide information on pathogenesis mechanism of and might be beneficial to the prevention of the pathogenesis of S. suis.