Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence.
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.
Chatterjee
Indranil
I
Department of Medical Microbiology, University of Saarland Hospital, Homburg/Saar, Germany. ichatterjee76@yahoo.com
Schmitt
Sigrid
S
Batzilla
Christoph F
CF
Engelmann
Susanne
S
Keller
Andreas
A
Ring
Michael W
MW
Kautenburger
Ralf
R
Ziebuhr
Wilma
W
Hecker
Michael
M
Preissner
Klaus T
KT
Bischoff
Markus
M
Proctor
Richard A
RA
Beck
Horst P
HP
Lenhof
Hans-Peter
HP
Somerville
Greg A
GA
Herrmann
Mathias
M
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
D001426:Bacterial Proteins; C087481:ClpC protein, Bacteria; D006360:Heat-Shock Proteins; D002244:Carbon