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

AdcR is a regulator controlling zinc transport in S. suis. Aranda and coauthors observed that disruption of this transcription factor can attenuate bacterial virulence in mouse model. 149 In contrast, Zur, the other zinc uptake regulator from 05ZYH33 strain of S. suis 2 is not essential for strong pathogenicity in porcine models. 29 Driven by the idea that host environment is critical for expression of bacterial virulence factors during the process of infection, Willenborg et al. 118 evaluated the effect of the sugar metabolism regulator catabolite control protein A (CcpA) on S. suis pathogenesis. As anticipated, expression levels of several virulence factors (such as ArcB, Sao, and Enolase) were altered in the ΔccpA mutant. Of particular note, a recent study implied that Sao protective antigen plays a limited role in bacterial virulence. 123 Moreover, the deletion of ccpA led to significant reduction of both capsule thickness and resistance to killing by porcine neutrophils 118 and impaired bacterial virulence. 119 ArgR, a member of ArgR/AhrC arginine repressor family, was recently proved to regulate expression of arcABC operon encoding an arginine deiminase system that is recognized as a putative virulence factor. 40, 146 Therefore, it is of interest to test the role of argR in S. suis virulence. Similar to the scenario observed with Rgg regulators present in other gram-positive pathogen, Zheng et al. defined an rgg-like ortholog in S. suis 05ZYH33, and observed its multiple roles in bacterial metabolism. More importantly, it was verified to be a virulence determinant of S. suis 2 in experimental models of piglets. 31 Interestingly, an H 2 O 2 -responsive Fur-like regulator, PerR was confirmed to determine bacterial virulence through regulating expression of both dpr, a Dps-like peroxide resistance protein-encoding gene, and metQIN encoding a methionine transporter. 150 Among the 15 putative two-component signal transduction systems in Chinese virulent strain of S. suis 2, 23 five have been proposed to be correlated with manifestation of strong virulence. 27, 42, 152, 153 In 2008, we reported the salK-salR system present in the 89K pathogenicity island. The deletion of this TCS system resulted in significant downregulation of 26 genes' expression level, and increased its susceptibility to polymorphonuclear leukocyte (PMN)-mediated killing. Consequently, the virulence of the ΔsalK-R mutant was seriously attenuated. 27 Shen et al. 158 conducted a follow-up study to address the regulatory network of SalK-SalR TCS system. As expected, proteomics-based investigation revealed 14 downregulated proteins and 1 upregulated protein, which partially agreed with our former microarray analysis. 158 To our much surprise, Zhong's group very recently elucidated the physiological role of this SalK-SalR TCS in regulating a bioactive lantibiotic suicin production, thereby replaced it with SuiK-SuiR. 151 Li and coworkers 42 reported the second TCS system, ciaK-ciaR, which is required for pathogenicity of SS2 in the infection models of both CD1 mice and piglets. Han et al. showed that Ihk/Irr TCS contributes to full virulence of Streptococcus suis serotype 2 strain 05ZYH33 via regulating bacterial cell metabolism. 152 Very recently, two more TCS (VirR/VirS 153 and NisK/ R 154 ) was demonstrated to be essential for SS2 pathogenicity.