Two-Component System Response Regulators Involved in Virulence of Streptococcus pneumoniae TIGR4 in Infective Endocarditis

Abstract

Streptococci resident in the oral cavity have been linked to infective endocarditis (IE). While other viridans streptococci are commonly studied in relation to IE, less research has been focused on Streptococcus pneumoniae. We established for the first time an animal model of S. pneumoniae IE, and examined the virulence of the TIGR4 strain in this model. We hypothesized that two-component systems (TCS) may mediate S. pneumoniae TIGR4 strain virulence in IE and examined TCS response regulator (RR) mutants of TIGR4 in vivo with the IE model. Thirteen of the 14 RR protein genes were mutagenized, excluding only the essential gene SP_1227. The requirement of the 13 RRs for S. pneumoniae competitiveness in the IE model was assessed in vivo through use of quantitative real-time PCR (qPCR) and competitive index assays. Using real-time PCR, several RR mutants were detected at significantly lower levels in infected heart valves compared with a control strain suggesting the respective RRs are candidate virulence factors for IE. The virulence reduction of the ΔciaR mutant was further confirmed by competitive index assay. Our data suggest that CiaR is a virulence factor of S. pneumoniae strain TIGR4 for IE.

The pneumococcal two-component system SirRH is linked to enhanced intracellular survival of Streptococcus pneumoniae in influenza-infected pulmonary cells

“…However, in the context of IAV infection, the hk01::ery mutant showed impaired pneumococcal intracellular survival compared to the wt strain ( Fig 1B), suggesting that their components participate in sensing the IAV-infected environment. The hk01:: ery mutant corresponds to TCS01, one of the least studied TCSs but previously identified as a virulent factor in S. pneumoniae [23][24][25]. TCS01, hereafter named SirRH (for stress-induced response), contains the SirH histidine kinase and the SirR response regulator.…”

Regulation of pneumococcal epigenetic and colony phases by multiple two-component regulatory systems

“…S. pneumoniae has 13 complete TCSs and an orphan regulator (RR14, RitR) [14][15][16]. Previous studies have shown that most of the TCSs are necessary for pneumococcal pathogenicity in animal models [15,17], but the precise functions for most of the TCSs are largely unknown.…”

Physiological Roles of the Dual Phosphate Transporter Systems in Low and High Phosphate Conditions and in Capsule Maintenance of Streptococcus pneumoniae D39

“…Therefore, the Pst1 and Pst2 transporters must mediate P i acquisition from several niches with vastly different P i concentrations in human hosts (Orihuela et al, 2001 ; Wilson, 2005 , 2008 ). Signature-tagged mutagenesis (STM) screens and a study of the role of the PnpR RR (also called RR04) indicated that the pnpRS, pst1 , and pst2 operons are all required for full pneumococcal virulence (Polissi et al, 1998 ; Throup et al, 2000 ; Hava and Camilli, 2002 ; McCluskey et al, 2004 ; Paterson et al, 2006 ; Trihn et al, 2013 ). Consistent with these earlier studies, a recent Tn-Seq study showed that PhoU1 is important for nasopharynx colonization, whereas PhoU2 is important for lung infection (van Opijnen and Camilli, 2012 ).…”