Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence
Staphylococcus aureus ClpC ATPase is a late growth phase effector of metabolism and persistence
复制标题
DOI：
10.1002/pmic.200800586
复制
发表时间：
2009-03-01
期刊：
影响因子：
3.4
通讯作者：
Herrmann, Mathias
中科院分区：
文献类型：
--
作者：
Chatterjee, Indranil;Schmitt, Sigrid;Herrmann, Mathias
金黄色葡萄球菌Clp ATP酶（分子伴侣）改变正常的生理功能，包括乌头酸酶介导的对静止后生长、醋酸钙释放和进入死亡期的作用（Chatterjee等人，J. Bacteriol. 2005，187，4488-4496）。在本研究中，使用DNA微阵列和2-D PAGE以及随后的MALDI-TOF MS检测了ClpC在生理、代谢和稳定期后期存活中的整体功能。结果表明，ClpC参与调节胚胎发生、戊糖-磷酸途径、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、严格反应和程序性细胞死亡。因此，ClpC的一个主要功能是平衡生长后期的碳代谢。此外，碳代谢的这些变化导致细胞内游离NADH浓度、细胞相关铁的量和脂肪酸代谢的改变。这项研究为ClpC作为葡萄球菌能量代谢，应激调节和后期稳定期存活的关键因素提供了强有力的证据;因此，这些数据为S.金黄色葡萄球菌在慢性感染中向持久状态发展。
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 at., 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.