Staphylococcus aureus SaeRS two-component system (SaeRS)

The Staphylococcus aureus SaeRS two-component system is a master regulatory network that controls the expression of numerous virulence factors, including alpha-hemolysin, leukocidins, and coagulase, which are vital for the pathogen's survival and evasion of the host immune system [1.2.1, 1.3.1]. The system consists of the sensor histidine kinase SaeS and the response regulator SaeR, which together sense environmental cues—such as human neutrophil peptides and hydrogen peroxide—to trigger a transcriptional response [1.2.1, 1.3.3]. Upon activation, SaeS autophosphorylates and transfers the phosphate group to SaeR, which then binds to specific DNA sequences to regulate gene expression [1.3.1, 1.3.3]. Because the SaeRS system is essential for staphylococcal pathogenesis but not for basic bacterial growth, it is considered a high-priority target for anti-virulence therapy [1.2.2, 1.4.1]. Inhibitors such as fenoprofen and phenazopyridine have been identified to disrupt this signaling pathway, effectively reducing the production of toxins and enhancing the host's ability to clear the infection [1.2.1, 1.4.3]. This anti-virulence approach aims to disarm the bacteria rather than kill them, potentially reducing the selective pressure for antibiotic resistance [1.4.1, 1.4.3].

Other names

SaeRS two-component systemSae systemSaeR/SStaphylococcus exoprotein expression systemSaeR regulatory system

Inhibition of sensor kinase autophosphorylation and inhibition of response regulator DNA binding