Akers Johnny C, Tan Ming
Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA.
J Bacteriol. 2006 Jun;188(12):4236-43. doi: 10.1128/JB.01660-05.
Tryptophan is an essential amino acid that is required for normal development in Chlamydia species, and tryptophan metabolism has been implicated in chlamydial persistence and tissue tropism. The ability to synthesize tryptophan is not universal among the Chlamydiaceae, but species that have a predicted tryptophan biosynthetic pathway also encode an ortholog of TrpR, a regulator of tryptophan metabolism in many gram-negative bacteria. We show that in Chlamydia trachomatis serovar D, TrpR regulates its own gene and trpB and trpA, the genes for the two subunits of tryptophan synthase. These three genes form an operon that is transcribed by the major form of chlamydial RNA polymerase. TrpR acts as a tryptophan-dependent aporepressor that binds specifically to operator sequences upstream of the trpRBA operon. We also found that TrpR repressed in vitro transcription of trpRBA in a promoter-specific manner, and the level of repression was dependent upon the concentrations of TrpR and tryptophan. Our findings provide a mechanism for chlamydiae to sense changes in tryptophan levels and to respond by modulating expression of the tryptophan biosynthesis genes, and we present a unified model that shows how C. trachomatis can combine transcriptional repression and attenuation to regulate intrachlamydial tryptophan levels. In the face of host defense mechanisms that limit tryptophan availability from the infected cell, the ability to maintain homeostatic control of intrachlamydial tryptophan levels is likely to play an important role in chlamydial pathogenesis.
色氨酸是衣原体属正常发育所必需的一种必需氨基酸，色氨酸代谢与衣原体的持续性和组织嗜性有关。在衣原体科中，并非所有物种都具备合成色氨酸的能力，但具有预测色氨酸生物合成途径的物种也编码TrpR的直系同源物，TrpR是许多革兰氏阴性菌中色氨酸代谢的调节因子。我们发现，在沙眼衣原体血清型D中，TrpR调控其自身基因以及色氨酸合酶两个亚基的基因trpB和trpA。这三个基因形成一个操纵子，由衣原体主要形式的RNA聚合酶转录。TrpR作为一种色氨酸依赖性的无辅基阻遏物，特异性结合trpRBA操纵子上游的操纵序列。我们还发现，TrpR以启动子特异性方式抑制trpRBA的体外转录，抑制水平取决于TrpR和色氨酸的浓度。我们的研究结果为衣原体感知色氨酸水平变化并通过调节色氨酸生物合成基因的表达做出反应提供了一种机制，并且我们提出了一个统一模型，展示了沙眼衣原体如何结合转录抑制和弱化来调节衣原体内部的色氨酸水平。面对限制被感染细胞中色氨酸可用性的宿主防御机制，维持衣原体内部色氨酸水平的稳态控制能力可能在衣原体发病机制中发挥重要作用。
