SaeRS two-component regulatory system (SaeRS)

The SaeRS two-component regulatory system is a critical signaling pathway in Staphylococcus aureus that controls the expression of over 20 major virulence factors, including alpha-hemolysin, coagulase, and various immune-evasion proteins (PMID: 21854221, 26150533). It consists of the sensor histidine kinase SaeS, which detects host-derived signals such as alpha-defensins and pH changes, and the response regulator SaeR, which acts as a transcription factor upon phosphorylation (PMID: 17114253). Because SaeRS is essential for the pathogenesis of S. aureus in various infection models, it has become a prominent target for anti-virulence therapy (PMID: 29133444). Inhibiting this system does not necessarily kill the bacteria but renders them less harmful and more susceptible to host immune clearance, potentially reducing the selective pressure for antibiotic resistance (PMID: 31515454). Current research focuses on small molecule inhibitors that disrupt the phosphorylation relay or the DNA-binding capability of SaeR to attenuate staphylococcal toxicity (PMID: 27524331).

Other names

SaeR/S systemS. aureus exoprotein expression systemSaeRS TCSStaphylococcus aureus exoprotein expression regulatory system

Inhibition of the sensor kinase SaeS autophosphorylation or interference with the DNA-binding activity of the response regulator SaeR to prevent the transcription of virulence genes.