Revelation of AbfR in regulation of mismatch repair and energy metabolism in S. epidermidis by integrated proteomic and metabolomic analysis

J Proteomics. 2020 Aug 30:226:103900. doi: 10.1016/j.jprot.2020.103900. Epub 2020 Jul 22.

Abstract

Staphylococcus epidermidis is a common causative of nosocomial infections associated with indwelling medical devices. To date, the mechanisms of the pathogenicity and drug resistance of S. epidermidis have not been clearly elucidated. AbfR has been previously identified as an oxidation-sensing regulator that regulates bacterial aggregation and biofilm formation by responding to oxidative stress in S. epidermidis; however, the regulatory pathways of AbfR are underexplored. In this study, we investigated the oxidation-sensing regulatory mechanism of AbfR using TMT10-plex labelling quantitative proteomic and untargeted metabolomic approaches. Integrated analysis of two omics datasets indicated that abfR depletion influenced nucleic acid metabolism and activated the DNA mismatch repair pathway. In addition, several energy-related metabolic pathways, including tricarboxylic acid (TCA) cycle, glycolysis, and arginine metabolism, were remarkably impacted by the deletion of abfR. This study revealed the regulatory networks of the transcription factor AbfR from a multi-omics view and demonstrated that AbfR played a broad role in not only mismatch repair but also energy metabolism, enabling S. epidermidis to constantly sense and adapt to environmental stress. SIGNIFICANCE: Staphylococcus epidermidis has emerged as a major nosocomial infection causing pathogen. AbfR, a transcription factor of S. epidermidis, plays an important role in oxidative stress, cell aggregation, and biofilm formation; however, the regulatory mechanism of AbfR is unknown. Using proteomic and metabolomic approaches, this study unveils the global regulatory networks of AbfR, and demonstrates that AbfR not only regulates the DNA mismatch repair pathway by an oxidation sensing mechanism but also affects energy metabolism. This study expands the body of knowledge related to regulatory transcription factors in staphylococci and lays a foundation for future research on clinical infections caused by S. epidermidis.

Keywords: AbfR transcription factor; Antibiotic resistance regulator; Oxidation-sensing regulator; Oxidative stress; Staphylococcus epidermidis; TMT10-plex labelling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism
  • Biofilms
  • Citric Acid Cycle
  • DNA Mismatch Repair
  • Humans
  • Proteomics
  • Staphylococcal Infections*
  • Staphylococcus epidermidis* / metabolism

Substances

  • Bacterial Proteins