Chiang-Ni Chuan, Chu Teng-Ping, Wu Jiunn-Jong, Chiu Cheng-Hsun
Department of Microbiology and Immunology, College of Medicine, Chang Gung UniversityTao-yuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung UniversityTao-Yuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial HospitalTao-yuan, Taiwan.
Department of Microbiology and Immunology, College of Medicine, Chang Gung University Tao-yuan, Taiwan.
Front Microbiol. 2016 Nov 29;7:1935. doi: 10.3389/fmicb.2016.01935. eCollection 2016.
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.
CovR/CovS是人类病原体A组链球菌（GAS）中一种重要的双组分调节系统。流行病学研究表明，传感激酶CovS的失活与侵袭性临床表现相关。在没有CovS的情况下，反应调节因子CovR的磷酸化水平显著降低，导致毒力因子表达的去抑制和细菌侵袭性增加。链球菌致热外毒素B（SpeB）是一种半胱氨酸蛋白酶，受CovR负调控；然而，在突变体中SpeB的表达几乎完全被抑制。本研究发现，在A20菌株中，未磷酸化的CovR作为SpeB阳性调节因子Rgg的转录抑制因子。此外，Rgg阴性调节因子LacD.1的表达在突变体中上调。这些结果表明，突变体中Rgg的失活将直接介导抑制作用。当前研究表明，在突变体中过表达而不是失活部分恢复了表达，表明在突变体中只有抑制作用，而不是上调作用，导致了抑制作用。
