Senescence of Staphylococci: The roles of Clp ATPases in bacterial metabolism, survival and persistence during late stationary phase

由金黄色葡萄球菌引起的疾病通常是慢性持续性的，这种感染很难治疗。金黄色葡萄球菌已经发展出多种应激反应系统，允许协调表达毒力因子和适应环境条件。用于蛋白质再激活和降解的atp酶/蛋白酶复合物是高度保守的系统，在应激反应中起主要作用。在各种细菌中，Clp复合物的作用与能力、细胞壁合成、毒力和其他生理特性有关。最近，在金黄色葡萄球菌中，各种Clp atp酶被发现影响全局调节功能，导致复杂的表型变化。我们已经证明，通过功能性TCA循环代谢，ClpC允许静止后再生和进入细菌死亡阶段，我们已经得出结论，ClpC可能在长期生存中发挥重要的调节作用。在这里，我们建议将ClpC与其他金黄色葡萄球菌Clp atp酶相比，在金黄色葡萄球菌衰老、存活和程序性细胞死亡等后期现象方面的作用进行扩展。利用代谢组学方法对调控修饰进行全局分析，将允许更详细地表征金黄色葡萄球菌ClpC。因此，计划中的研究将有助于揭示Clp atp酶在慢性疾病过程中的假定作用。

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. We have shown that ClpC allows for poststationary regrowth and entry into the bacterial death phase through a functional TCA cycle metabolism, and we have concluded that ClpC may play a major regulatory role for long-term survival. Here we propose to extend the characterization of the role of ClpC compared to other S. aureus Clp ATPases with respect to late phase phenomena such as S. aureus senescence, survival, and programmed cell death. Global analyses of regulatory modifications with a metabolomic approach will allow to characterize S. aureus ClpC in further detail. Planned studies will thus help to unravel the putative role of Clp ATPases in chronicpersistent course of disease.