Revealing Regulatory Networks Of Transcription Factor AbfR In Staphylococcus Epidermidis By Integration Of Proteomics And Metabolomics

Staphylococcus epidermidis is the most prevalent commensal bacterium on human skin and also serves as a major cause of nosocomial infections associating with the use of implanted biomaterials.The mechanisms of its pathogenicity and drug resistance are still not elucidated clearly.Bacteria usually have to evade the oxidative killing by toxic reactive oxygen species(ROS),which generated by innate immune cells or the normal course of aerobic metabolism.AbfR is a novel oxidation-sensing transcription factor which belongs to MarR family in Staphylococcus epidermidis.AbfR plays a significant role in oxidative stress,cell auto-aggregation and biofilm formation,but its regulatory mechanisms are underexplored yet.Herein,we investigated the oxidation-sensing regulatory mechanism of AbfR through utilizing the TMT10 plex labelling quantitative proteomic and untargeted metabolomic approaches.Proteomic data shows depletion of AbfR activates the PIA synthesis and biofilm formation through regulations to multiple significant regulators such as IcaADBC and agr system.Biofilm formation assay confirms that AbfR is the inhibitor of Staphylococcus epidermidis biofilm formation.Integrated analysis of the two omics data indicates that depletion of abfR influenced the nucleic acid metabolism,of which the DNA mismatch repair pathway was significantly activated.EMSA further demonstrates that AbfR regulates this pathway through directly regulating transcription of mutS by oxidation sensing mechanism to resist ROS damage.In addition,several energy-related metabolic pathways including tricarboxylic acid(TCA)cycle,glycolysis,and arginine metabolism are significantly impacted by deleting abfR.This is the first study combining proteomic and metabolomic tools in Staphylococcus epidermidis research.Herein,we reveal the regulatory networks of the novel regulator AbfR from a multi-omics view,uncovering the molecular mechanism how AbfR impacts biofilm formation.We also demonstrate that AbfR plays a broad role in not only mismatch repair but also energy metabolism,which allows Staphylococcus epidermidis constantly to sense and adapt to environmental stress.This study expands the knowledge of Staphylococci and lays a foundation for future searches for clinic treatment of infection caused by Staphylococcus epidermidis.