Repression of Rgg But Not Upregulation of LacD.1 in -type Mutant Mediates the SpeB Repression in Group A .

CovR/CovS is an important two-component regulatory system in human pathogen group A (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 mutant. The present study found that in the 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 mutant. These results suggest that inactivation of Rgg in the mutant would directly mediate repression. The current study showed that overexpression of but not inactivation of in the mutant partially restores expression, indicating that only repression, but not upregulation, contributes to the repression in the mutant.