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, SS2) has evolved into a highly infectious entity, which caused the two recent large-scale outbreaks of human SS2 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 Findings89K is a newly predicted pathogenicity island (PAI) which is specific to Chinese epidemic strains isolated from these two SS2 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 salKR eliminated the lethality of SS2 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/SignificanceThese findings suggest that SalK/SalR is requisite for the full virulence of ethnic Chinese isolates of highly pathogenic SS2, thus providing experimental evidence for the validity of this bioinformatically predicted PAI.

Two novel regulators of N‐acetyl‐galactosamine utilization pathway and distinct roles in bacterial infections

“…2008; Li et al. 2008). As we performed before (Feng and Cronan 2009, 2010), RNA integrity/quality was validated by separation of 1.0% agarose gel electrophoresis.…”

The Streptococcus suis transcriptional landscape reveals adaptation mechanisms in pig blood and cerebrospinal fluid

“…Research on gene regulation has focused mainly on protein regulators such as two-component or stand-alone regulators, including LuxS , CcpA , CovR ), CiaR/H , Ihk/Irr (Han et al 2012), AdcR (Aranda et al 2009b), ArgR , SalK/R (Li et al 2008), RevSC21 ), and Rgg . Recent studies, however, have revealed that regulatory RNAs (small RNAs from intergenic regions [sRNAs] and antisense RNA [asRNA]) have emerged as key regulators of virulence in several bacteria (Romby et al 2006;ToledoArana et al 2009;Waters and Storz 2009;Sharma et al 2010;Wurtzel et al 2012).…”

Research progress in China on the virulence factors of Streptococcus suis serotype

“…Li et al (22) showed that the SalKR mutant strain had no pathogenicity in the piglet infection experiment. On the contrary, functional complementation of salKR into the isogenic salKR mutant strain restored its high pathogenicity.…”