Department of Civil and Environmental Engineering, University of Michigan, 2350 Hayward Street, 2340 GG Brown, Ann Arbor, MI 48109-2125, USA.
Mol Microbiol. 2011 Mar;79(6):1547-56. doi: 10.1111/j.1365-2958.2011.07544.x. Epub 2011 Feb 15.
NalC is a TetR type regulator that represses the multidrug efflux pump MexAB-OprM in Pseudomonas aeruginosa. Here we explain the mechanism of NalC-mediated regulation of MexAB-OprM. We show that NalC non-covalently binds chlorinated phenols and chemicals containing chlorophenol side-chains such as triclosan. NalC-chlorinated phenol binding results in its dissociation from promoter DNA and upregulation of NalC's downstream targets, including the MexR antirepressor ArmR. ArmR upregulation and MexR-ArmR complex formation have previously been shown to upregulate MexAB-OprM. In vivo mexB and armR expression analyses were used to corroborate in vitro NalC-chlorinated phenol binding. We also show that the interaction between chlorinated phenols and NalC is reversible, such that removal of these chemicals restored NalC promoter DNA binding. Thus, the NalC-chlorinated phenol interaction is likely a pertinent physiological mechanism that P. aeruginosa uses to control expression of the MexAB-OprM efflux pump.
NalC 是一种 TetR 型调控因子，可抑制铜绿假单胞菌中的多药外排泵 MexAB-OprM。在这里，我们解释了 NalC 介导的 MexAB-OprM 调节机制。我们表明，NalC 非共价结合氯化酚和含有氯苯侧链的化学物质，如三氯生。NalC-氯化酚结合导致其从启动子 DNA 解离，并上调 NalC 的下游靶标，包括 MexR 反阻遏物 ArmR。先前已经表明，ArmR 的上调和 MexR-ArmR 复合物的形成会上调 MexAB-OprM。体内 mexB 和 armR 表达分析用于证实体外 NalC-氯化酚结合。我们还表明，氯化酚与 NalC 之间的相互作用是可逆的，因此去除这些化学物质会恢复 NalC 启动子 DNA 结合。因此，NalC-氯化酚相互作用可能是铜绿假单胞菌用来控制 MexAB-OprM 外排泵表达的一种相关生理机制。
