title: Life and death of proteins: a case study of glucose-starved Staphylococcus aureus.
abstract: 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.
authors.affiliation: Institute of Microbiology, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Michalik
authors.forename: Jörg
authors.initials: J
authors.lastname: Bernhardt
authors.forename: Andreas
authors.initials: A
authors.lastname: Otto
authors.forename: Martin
authors.initials: M
authors.lastname: Moche
authors.forename: Dörte
authors.initials: D
authors.lastname: Becher
authors.forename: Hanna
authors.initials: H
authors.lastname: Meyer
authors.forename: Michael
authors.initials: M
authors.lastname: Lalk
authors.forename: Claudia
authors.initials: C
authors.lastname: Schurmann
authors.forename: Rabea
authors.initials: R
authors.lastname: Schlüter
authors.forename: Holger
authors.initials: H
authors.lastname: Kock
authors.forename: Ulf
authors.initials: U
authors.lastname: Gerth
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002952:Citric Acid Cycle; D049071:Endopeptidase Clp / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D009154:Mutation; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D059748:Proteolysis; D012097:Repressor Proteins / Q000037:antagonists & inhibitors; D013211:Staphylococcus aureus / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C540555:CodY protein, Staphylococcus aureus; D012097:Repressor Proteins; D049071:Endopeptidase Clp; D005947:Glucose