Structural and Functional Studies on the Virulence Regulators SaeR/S in Staphylococcus aureus

Staphylococcus aureus is both a commensal and a major Gram-positive human pathogen. S. aureus causes a wide spectrum of diseases ranging from minor skin infections to life-threatening conditions such as sepsis. Its pathogenic versatility is due partly to the production of numerous virulence factors, such as surface- and cell-associated proteins, secreted toxins, and enzyme proteins. The SaeR/S two-component system (TCS) of S. aureus controls the expression of major virulence factors including coagulase, -, - and -hemolysins, nuclease, and fibrinogen-binding proteins. Moreover, the SaeR/S gene regulatory system is reported to be highly related to S. aureus innate immune evasion, promoting bacterial survival and enhancing host mortality. The two-component systems are prototypical signal transduction mechanisms by which bacteria and lower eukaryotes monitor and respond to environmental stimuli. SaeS is a histidine kinase that regulates the phosphorylation status of its cognate response regulator protein SaeR to control target genes transcription to play a distinct role in S. aureus pathogenesis. In this study, we aim to purify SaeR and cytoplasmic domain of SaeS form Escherichia coli expression system and subsequently use the X-ray crystallographic and biophysical methods to investigate into the regulation of virulence factors of S. aureus.