SalK/SalR, a two-component signal transduction system, is essential for full virulence of highly invasive Streptococcus suis serotype 2

Abstract

Background: Streptococcus suis serotype 2 (S. suis 2 5S2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human 5S2 epidemic in China, and is characterized by a toxic shock-like syndrome. However, the molecular pathogenesis of this new emerging pathogen is still poorly understood. Methodology/Principal Findings: 89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two 5S2 outbreaks. Further bioinformatics analysis revealed a unique two-component signal transduction system (TCSTS) located in the candidate 89K PAI, which is orthologous to the SalK/SalR regulatory system of Streptococcus salivarius. Knockout of solKR eliminated the lethality of 5S2 in experimental infection of piglets. Functional complementation of salKR into the isogenic mutant ΔsalKR restored its soaring pathogenicity. Colonization experiments showed that the ΔsalKR mutant could not colonize any susceptible tissue of piglets when administered alone. Bactericidal assays demonstrated that resistance of the mutant to polymorphonuclear leukocyte (PMN)-mediated killing was greatly decreased. Expression microarray analysis exhibited a transcription profile alteration of 26 various genes down-regulated in the ΔsalKR mutant. Conclusions/Significance: These findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic 5S2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI. © 2008 Li et al.