Chatterjee Indranil, Schmitt Sigrid, Batzilla Christoph F, Engelmann Susanne, Keller Andreas, Ring Michael W, Kautenburger Ralf, Ziebuhr Wilma, Hecker Michael, Preissner Klaus T, Bischoff Markus, Proctor Richard A, Beck Horst P, Lenhof Hans-Peter, Somerville Greg A, Herrmann Mathias
Department of Medical Microbiology, University of Saarland Hospital, Homburg/Saar, Germany.
Proteomics. 2009 Mar;9(5):1152-76. doi: 10.1002/pmic.200800586.
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.
金黄色葡萄球菌Clp ATP酶（分子伴侣）会改变正常生理功能，包括对稳定期后生长、乙酸分解代谢以及进入死亡期产生的乌头酸酶介导效应（Chatterjee等人，《细菌学杂志》，2005年，第187卷，第4488 - 4496页）。在本研究中，利用DNA微阵列和二维聚丙烯酰胺凝胶电泳（2 - D PAGE）结合基质辅助激光解吸电离飞行时间质谱（MALDI - TOF MS），研究了ClpC在生理、代谢以及稳定期末期存活方面的整体功能。结果表明，ClpC参与调节糖异生、磷酸戊糖途径、丙酮酸代谢、电子传递链、核苷酸代谢、氧化应激、金属离子稳态、严紧反应以及程序性细胞死亡相关基因和/或蛋白质的表达。因此，ClpC的一个主要功能是平衡生长后期的碳代谢。此外，碳代谢的这些变化会导致细胞内游离NADH浓度、细胞相关铁含量以及脂肪酸代谢的改变。本研究为ClpC作为葡萄球菌能量代谢、应激调节以及稳定期末期存活的关键因素提供了有力证据；因此，这些数据为金黄色葡萄球菌在慢性感染中向持留菌状态的适应提供了重要见解。
