Impact of Staphylococcus aureus ClpC on late-stationary phase events involved in carbon metabolism, oxidative stress response, programmed cell death, and fatty acid metabolism: A combined proteomics and transcriptomics approach

  • Indranil Chatterjee, Department of Medical Microbiology, University of Saarland Hospital, Homburg/Saar, Germany
  • Dr S Schmitt, Institute for Biochemistry, University of Giessen, Giessen, Germany
  • Dr C Batzilla, Institute for Molecular Infectious Biology, Department of Medical Microbiology, University of Würzburg, Würzburg, Germany
  • A Keller, Center for Bioinformatics, University of Saarland, Saarbrücken, Germany
  • M Ring, Institute of Pharmaceutical Biotechnology, University of Saarland, Saarbrücken, Germany
  • Dr S Engelmann, Institute for Microbiology and Molecular Biology, University of Greifswald, Greifswald, Germany
  • Dr G Somerville, Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, United States
  • Prof Mathias Herrmann, Department of Medical Microbiology, University of Saarland Hospital, Homburg/Saar, Germany

    • Objective: We have previously shown that Clp ATPases influences cellular physiology functions including an aconitase-mediated effect on post-stationary-growth, acetate catabolism and entry into death phase (Chatterjee et al., 2005) which was further related to the persistence of S. aureus thymidine-dependent small colony variants (Chatterjee et al., 2007; 2008). Current study further dissects the role of ClpC on physiology, metabolism and late-stationary phase survival in S. aureus. Methods: DNA microarrays and global proteomic analysis were used to determine differential gene and protein expression patterns of the S. aureus WT and its clpC mutant during late stationary phases (76 h). Results: Inactivation of clpC led to a strong altered regulation of carbon metabolism. This was indicated through an increase in expression of the genes and/or proteins of numerous enzymes in the WT strain participating in the functioning of events such as gluconeogenesis, phosphate-pentose pathway, electron transport chain, oxidative stress and metal ion homeostatis. Furthermore, the combined data prove that S. aureus WT and its clpC mutant differs with respect to the level of unbound NADH production, the amount of cell-associated iron content and expression of genes/proteins involved in nutrient starvation and induction of programmed cell death. Most remarkably, the clpC mutant adapted its fatty acid metabolism for persistence during the late-stationary phase. Metabolic pathway analysis further confirmed our results. Conclusions: ClpC may be a key element for staphylococcal adaptation, particularly during prolonged times of bacterial life such as encountered in sessile and/or persistent staphylococcal populations.