Life and death of proteins: a case study of glucose-starved Staphylococcus aureus

Mol Cell Proteomics. 2012 Sep;11(9):558-70. doi: 10.1074/mcp.M112.017004. Epub 2012 May 3.


The cellular amount of proteins not only depends on synthesis but also on degradation. Here, we expand the understanding of differential protein levels by complementing synthesis data with a proteome-wide, mass spectrometry-based stable isotope labeling with amino acids in cell culture analysis of protein degradation in the human pathogen Staphylococcus aureus during glucose starvation. Monitoring protein stability profiles in a wild type and an isogenic clpP protease mutant revealed that 1) proteolysis mainly affected proteins with vegetative functions, anabolic and selected catabolic enzymes, whereas the expression of TCA cycle and gluconeogenesis enzymes increased; 2) most proteins were prone to aggregation in the clpP mutant; 3) the absence of ClpP correlated with protein denaturation and oxidative stress responses, deregulation of virulence factors and a CodY repression. We suggest that degradation of redundant, inactive proteins disintegrated from functional complexes and thereby amenable to proteolytic attack is a fundamental cellular process in all organisms to regain nutrients and guarantee protein homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / metabolism*
  • Citric Acid Cycle
  • Endopeptidase Clp / genetics
  • Endopeptidase Clp / metabolism
  • Gene Expression Regulation, Bacterial
  • Gluconeogenesis
  • Glucose / metabolism*
  • Mutation
  • Oxidative Stress
  • Protein Biosynthesis
  • Proteolysis
  • Repressor Proteins / antagonists & inhibitors
  • Staphylococcus aureus / enzymology
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / metabolism*


  • Bacterial Proteins
  • CodY protein, Staphylococcus aureus
  • Repressor Proteins
  • Endopeptidase Clp
  • Glucose