Streptococcus suis infection: An emerging/reemerging challenge of bacterial infectious diseases?

Feng, Youjun; Zhang, Huimin; Wu, Zuowei; Wang, Shihua; Cao, Min; Hu, Dan; Wang, Changjun

Surface/secreted components For Subgroup 1, a total of 17 genes/gene clusters have been determined thus far to contribute to bacterial pathogenicity ( 105, 106 plus implication into bacterial meningitis, 107 11 more members have been supplemented into this group that include SspA, the surface-associated subtilisin-like serine protease, 41, 108, 109 HtpS, a novel immunogenic cell surface-exposed protein, 110 and Sat surface protein 111, 112 (Table 2) . Like FBP, 103 the gene SSU05_1311 with unknown function was determined to be one more surface anchored fibronectin-binding protein. More importantly, this surface protein functions in vivo in crossing the mucosal epithelia to disseminate, suggesting it is a novel virulence factor. 113 Two independent research groups (one from Canada 41 and another from China 114 ) identified the subtilisin-like protease (SspA)-encoding gene (sspA, SSU0757) from the S. suis organism by screening the mutant library and genomic expression library, respectively. SspA proteinase possesses a typical cell wall anchoring signal, LPXTG, at its C-terminus, implying it is a cell surface-displayed protein. 108 Infection assays have demonstrated that SspA protein plays critical roles in SS2 pathogenicity. 108, 109, 114 A subsequent study further revealed that S. suis SspA protease might modulate cytokine secretion by macrophages, and thus trigger central nervous system inflammation associated with bacterial meningitis, frequently observed in SS2-infected patients as well as piglets. 41 HP0197 is a new a surface protective antigen that was originally identified by Jin's group in 2009. This immunogenic antigen can elicit obvious humoral antibody response and confer efficient protection against SS2 challenge in the infection models of both mice and pigs. 115 Subsequently, HP0197 protein was found to interact with host cell surface glycosaminoglycans (GAGs), and the binding sites were further proved by solving the X-ray structure of N-terminal GAG-binding domain combined with site-directed mutagenesis plus indirect immunofluorescence assay. 116 Very recently, the same research group reported that HP0197 is involved in bacterial virulence by evaluating the performance of the isogenic mutant Δhp0197 in both mice and pigs. 117 A reasonable interpretation would be that virulence attenuation is due to easier clearance of the Δhp0197 mutant by host immunological system during the stage of infection, and the fast clearance is attributed to the reduced CPS thickness and decreased resistance to phagocytosis. 117 Further comparative transcriptomics-based analyses elucidated that expression of CPS synthetic operon is downregulated in the Δhp0197 mutant relative to the wild-type strain. 117 Also the introduction of plasmid-borne hp0197 gene into the Δhp0197 mutant can restore the decreased expression level of cps operon to those seen with the wild type strain. 117 This observation is consistent with the fact that CcpA, a global carbon catabolite regulator, contributes to bacterial infectivity/pathogenicity. 118, 119 Preliminary evidence pointed out that HP0197 might determine the Ser-46 phosphorylation level of phospho carrier protein (HPr-46), a partner protein of CcpA in binding the catabolite-responsive elements (cre) of the target operons. Together, it suggested that integration of the posttranslational modification of HPr-46 and CcpA-mediated transcriptional regulation is linked to regulatory network of bacterial virulence.