Patton Toni G, Yang Soo-Jin, Bayles Kenneth W
Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, 83844-3052, USA.
Mol Microbiol. 2006 Mar;59(5):1395-404. doi: 10.1111/j.1365-2958.2006.05034.x.
The Staphylococcus aureus cidABC and lrgAB operons have been shown to play a key role in the regulation of murein hydrolase activity and cell death in a manner thought to be analogous to bacteriophage-encoded holins and anti-holins respectively. Because of these functions, it has been proposed that the regulation of these operons is tightly controlled and responsive to key metabolic signals. The current study revealed the presence of two overlapping regulatory pathways controlling cidABC and lrgAB expression, one dependent on acetic acid and the other dependent on proton motive force (PMF). The latter pathway was analysed using agents that affect various aspects of the PMF. Gramicidin and carbonyl cyanide m-chlorophenylhydrazone (CCCP), antimicrobial agents that dissipate the DeltapH and membrane potential (DeltaPsi), both enhanced lrgAB expression. Restoration of the PMF by incubation of the bacteria in the presence of glucose restored lrgAB expression back to the uninduced state. In addition, valinomycin, which specifically collapses the DeltaPsi, also induced lrgAB expression. In contrast, nigericin, which dissipates the DeltapH component of the PMF, was found to have a minimal effect on DeltaPsi and lrgAB transcription. Finally, the DeltaPsi-inducible expression of lrgAB was shown to be dependent on the previously characterized LytSR two-component regulatory system that is involved in the regulation of autolysis. The results of this study support a model in which the LytSR regulatory system responds to a collapse in DeltaPsi by inducing the transcription of the lrgAB operon.
金黄色葡萄球菌的cidABC和lrgAB操纵子已被证明在胞壁质水解酶活性调节和细胞死亡中起关键作用，其方式分别被认为类似于噬菌体编码的孔蛋白和抗孔蛋白。由于这些功能，有人提出这些操纵子的调节受到严格控制并对关键代谢信号作出反应。当前的研究揭示了存在两条重叠的调节途径来控制cidABC和lrgAB的表达，一条依赖于乙酸，另一条依赖于质子动力势（PMF）。使用影响PMF各个方面的试剂对后一条途径进行了分析。短杆菌肽和羰基氰化物间氯苯腙（CCCP），这两种能消除ΔpH和膜电位（ΔΨ）的抗菌剂，都增强了lrgAB的表达。通过在葡萄糖存在下孵育细菌来恢复PMF，可使lrgAB表达恢复到未诱导状态。此外，特异性消除ΔΨ的缬氨霉素也诱导了lrgAB的表达。相反，消除PMF的ΔpH成分的尼日利亚菌素被发现对ΔΨ和lrgAB转录的影响最小。最后，lrgAB的ΔΨ诱导型表达被证明依赖于先前已鉴定的参与自溶调节的LytSR双组分调节系统。这项研究的结果支持了一个模型，即LytSR调节系统通过诱导lrgAB操纵子的转录来响应ΔΨ的崩溃。
