The Gram-positive bacterium, Streptococcus suis serotype 2 (S. suis 2, SS2), is a major

zoonotic pathogen that causes meningitis and sepsis in humans, as well as a range of life-threatening infections including meningitis, arthritis, septicaemia and sudden death in piglets (Lun et al., 2007). Additionally, SS2 is the known causative agent of two recent large-scale Saracatinib research buy outbreaks of lethal human infections associated with streptococcal toxic-shock-like syndrome in China, which raised a major concern for global public health (Tang et al., 2006). Recent sporadic cases in neighbouring countries, including Vietnam and Thailand, suggest that SS2 remains a serious threat for another epidemic. In view of the growing significance of such infections, the pathogenesis of this emerging pathogen has been the subject of ongoing interest in the social and public health fields in recent years. It is well known that bacterial two-component systems (TCSs) can coordinately regulate many genes to adapt to and survive in constantly changing environmental conditions (Krell et al., 2010). Identification of the target genes Target Selective Inhibitor Library cell line regulated by TCSs can provide important

insights towards understanding the virulence mechanisms of pathogens. Using genomic-based approaches, 15 TCSs were previously identified in the genome of S. suis 05ZYH33 (Chen et al., 2007). To date, only four of them have been described, but the precise regulatory mechanisms of many of them remain unclear. The RevS orphan response regulator has been identified as the first TCS involved in the pathogenesis of SS2 infections in piglets (de Greeff et al., 2002). SalK/SalR is a TCS located in the 89K pathogenicity island (PAI) that is specific to Chinese epidemic SS2 strains, and was proved to be essential

for full virulence of highly pathogenic SS2 (Li et al., 2008). CovR is an orphan response regulator reported to negatively control the virulence of SS2 and regulate the expression of many proven or putative virulence factors, such as capsular Interleukin-3 receptor polysaccharide (CPS), sortase A, streptodornase, laminin-binding protein and haemolysin (Pan et al., 2009). CiaRH is a recently characterized TCS implicated in the virulence of SS2 in both murine and pig infection models (Li et al., 2011). To obtain a more detailed picture of the global regulation of SS2 virulence, the roles of the other uncharacterized SS2 TCSs need further investigations. In this study, we present the first insight into the role of the VirR/VirS system in the pathogenesis of S. suis 05ZYH33, which is orthologous to a global regulator of various toxins and enzymes in Clostridium perfringens (Lyristis et al., 1994; Shimizu et al., 1994). An isogenic knockout mutant of VirR/VirS was constructed, and the effects of the deletion on the characteristics of SS2 both in vitro and in vivo were examined.