Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence |
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| Authors: | Indranil Chatterjee Dr. Sigrid Schmitt Christoph F. Batzilla Susanne Engelmann Andreas Keller Michael W. Ring Ralf Kautenburger Wilma Ziebuhr Michael Hecker Klaus T. Preissner Markus Bischoff Richard A. Proctor Horst P. Beck Hans‐Peter Lenhof Greg A. Somerville Mathias Herrmann |
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| Affiliation: | 1. Department of Medical Microbiology, University of Saarland Hospital, Homburg/Saar, Germany;2. Institute for Biochemistry, University of Giessen, Giessen, Germany;3. Both the authors contributed equally to this work.;4. Department of Medical Microbiology, Institute for Molecular Infectious Biology, University of Würzburg, Würzburg, Germany;5. Institute for Microbiology and Molecular Biology, University of Greifswald, Greifswald, Germany;6. Center for Bioinformatics, University of Saarland, Saarbrücken, Germany;7. Institute of Pharmaceutical Biotechnology, University of Saarland, Saarbrücken, Germany;8. Institute of Inorganic and Analytical Chemistry and Radiochemistry, University of Saarland, Saarbrücken, Germany;9. Departments of Microbiology, Immunology and Medicine, University of Wisconsin, Madison, WI, USA;10. Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, NE, USA |
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| Abstract: | Staphylococcus aureus Clp ATPases (molecular chaperones) alter normal physiological functions including an aconitase‐mediated effect on post‐stationary growth, acetate catabolism, and entry into death phase (Chatterjee et al., J. Bacteriol. 2005, 187, 4488–4496). In the present study, the global function of ClpC in physiology, metabolism, and late‐stationary phase survival was examined using DNA microarrays and 2‐D PAGE followed by MALDI‐TOF MS. The results suggest that ClpC is involved in regulating the expression of genes and/or proteins of gluconeogenesis, the pentose‐phosphate pathway, pyruvate metabolism, the electron transport chain, nucleotide metabolism, oxidative stress, metal ion homeostasis, stringent response, and programmed cell death. Thus, one major function of ClpC is balancing late growth phase carbon metabolism. Furthermore, these changes in carbon metabolism result in alterations of the intracellular concentration of free NADH, the amount of cell‐associated iron, and fatty acid metabolism. This study provides strong evidence for ClpC as a critical factor in staphylococcal energy metabolism, stress regulation, and late‐stationary phase survival; therefore, these data provide important insight into the adaptation of S. aureus toward a persister state in chronic infections. |
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| Keywords: | ClpC Metabolism Persistence Staphylococcus aureus Tricarboxylic acid cycle |
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