title: Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence.
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.
authors.affiliation: Department of Medical Microbiology, University of Saarland Hospital, Homburg/Saar, Germany. ichatterjee76@yahoo.com
authors.forename: Indranil
authors.initials: I
authors.lastname: Chatterjee
authors.forename: Sigrid
authors.initials: S
authors.lastname: Schmitt
authors.forename: Christoph F
authors.initials: CF
authors.lastname: Batzilla
authors.forename: Susanne
authors.initials: S
authors.lastname: Engelmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Keller
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ring
authors.forename: Ralf
authors.initials: R
authors.lastname: Kautenburger
authors.forename: Wilma
authors.initials: W
authors.lastname: Ziebuhr
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.forename: Markus
authors.initials: M
authors.lastname: Bischoff
authors.forename: Richard A
authors.initials: RA
authors.lastname: Proctor
authors.forename: Horst P
authors.initials: HP
authors.lastname: Beck
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Lenhof
authors.forename: Greg A
authors.initials: GA
authors.lastname: Somerville
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
mesh_terms: D001426:Bacterial Proteins / Q000502:physiology*; D002244:Carbon / Q000378:metabolism / Q000502:physiology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000502:physiology*; D053858:Metabolic Networks and Pathways / Q000502:physiology; D010641:Phenotype; D013211:Staphylococcus aureus / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; C087481:ClpC protein, Bacteria; D006360:Heat-Shock Proteins; D002244:Carbon