Abstract
CovR/CovS is an important two-component regulatory system in human pathogen group A Streptococcus (GAS). Epidemiological studies have shown that inactivation of the sensor kinase CovS is correlated with invasive clinical manifestations. The phosphorylation level of response regulator CovR decreases dramatically in the absence of CovS, resulting in the derepression of virulence factor expression and an increase in bacterial invasiveness. Streptococcal pyrogenic exotoxin B (SpeB) is a cysteine protease and is negatively regulated by CovR; however, the expression of SpeB is almost completely repressed in the covS mutant. The present study found that in the emm1-type A20 strain, non-phosphorylated CovR acts as a transcriptional repressor for SpeB-positive regulator Rgg. In addition, the expression of Rgg-negative regulator LacD.1 is upregulated in the covS mutant. These results suggest that inactivation of Rgg in the covS mutant would directly mediate speB repression. The current study showed that overexpression of rgg but not inactivation of lacD.1 in the covS mutant partially restores speB expression, indicating that only rgg repression, but not lacD.1 upregulation, contributes to the speB repression in the covS mutant.
Highlights
Streptococcus pyogenes is an important human pathogen causing diseases including pharyngitis, tonsillitis, scarlet fever, cellulitis, necrotizing fasciitis, and toxic shock syndrome
These results suggest that CovR acts as a repressor of speB expression, even in the absence of sensor kinase CovS
SW934, but not AP3, hydrolyzed casein in the skim-milk agar plate (Figure 1B, lower panel). These results indicate that CovR acts as a negative regulator of speB expression in both wild type and covS mutant strains
Summary
Streptococcus pyogenes (group A Streptococcus, GAS) is an important human pathogen causing diseases including pharyngitis, tonsillitis, scarlet fever, cellulitis, necrotizing fasciitis, and toxic shock syndrome. Mutations in the covS gene are detected more frequently in clinical isolates from severe invasive infections than in non-invasive isolates (Sumby et al, 2006; Ato et al, 2008; Ikebe et al, 2010; Lin et al, 2014; Friaes et al, 2015). Acquisition of null covS alleles causes a repression of streptococcal pyrogenic exotoxin B (SpeB) and upregulation of many virulence factor-encoding genes, resulting in increased GAS virulence during infection (Sumby et al, 2006; Walker et al, 2007; Ikebe et al, 2010; Friaes et al, 2015).
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