Senescence of staphylococci: using functional genomics to unravel the roles of ClpC ATPase during late stationary phase

Abstract

Disease caused by Staphylococcus aureus frequently takes a chronic persistent course, and such infections are difficult to treat. S. aureus has developed various stress response systems allowing for coordinated expression of virulence factors and adaptation to environmental conditions. Clp ATPase/protease complexes for protein reactivation and degradation are highly conserved systems with a primary function in stress response. In various bacterial species, the role of Clp complexes has been associated with competence, cell wall synthesis, virulence and other physiologic properties. More recently, in S. aureus various Clp ATPases have been found to influence global regulator functions resulting in complex phenotypic changes. In this review, we briefly outline current knowledge including our own work with ClpC ATPase. We could highlight an important role of ClpC that allows for post-stationary regrowth and entry into the bacterial death phase through a functional tricarboxylic acid (TCA) cycle metabolism. We have concluded that ClpC may play a major regulatory role for long-term survival. Furthermore, using functional genomics data, we could extend the global characterization of the functions of ClpC in S. aureus with respect to late-phase phenomena such as S. aureus carbon metabolism, ion homeostasis, oxidative stress response, survival, and programmed cell death. These studies will thus help to further unravel the putative role of Clp ATPases in the chronic-persistent course of disease.