Wood Heidi, Fehlner-Gardner Christine, Berry Jody, Fischer Elizabeth, Graham Bonnie, Hackstadt Ted, Roshick Christine, McClarty Grant
National Microbiology Laboratory, Health Canada, 1015 Arlington Street, Winnipeg, Manitoba, Canada R3T 2N2.
Mol Microbiol. 2003 Sep;49(5):1347-59. doi: 10.1046/j.1365-2958.2003.03638.x.
We previously reported that Chlamydia trachomatis expresses the genes encoding tryptophan synthase (trpA and trpB). The results presented here indicate that C. trachomatis also expresses the tryptophan repressor gene (trpR). The complement of genes regulated by tryptophan levels in C. trachomatis is limited to trpBA and trpR. trp gene expression was repressed if chlamydiae-infected HeLa cells were cultured the presence of tryptophan and induced if grown in tryptophan-depleted medium or in the presence of IFN-gamma. Furthermore, expression of the trp genes in strains which encode a functional tryptophan synthase is repressed when infected cells are cultured in the presence of the tryptophan precursor indole. Results from experiments with cycloheximide, an inhibitor of eukaryotic protein synthesis, indicate that in addition to the absolute size of the intracellular tryptophan pool, host competition for available tryptophan plays a key role in regulating expression of the trp genes. The tryptophan analogue, 5-fluorotryptophan, repressed trp gene expression and induced the formation of aberrant organisms of C. trachomatis. The growth-inhibitory properties of 5-fluorotryptophan could be reversed with exogenous tryptophan but not indole. In total, our results indicate that the ability to regulate trp gene expression in response to tryptophan availability is advantageous for the intracellular survival of this organism. Furthermore, the fact that C. trachomatis has retained the capacity to respond to tryptophan limitation supports the view that the in vivo antichlamydial effect of IFN-gamma is via the induction of the tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase.
我们之前报道过沙眼衣原体表达编码色氨酸合成酶的基因（trpA和trpB）。此处呈现的结果表明沙眼衣原体也表达色氨酸阻遏基因（trpR）。沙眼衣原体中受色氨酸水平调控的基因互补物仅限于trpBA和trpR。如果在色氨酸存在的情况下培养感染了衣原体的HeLa细胞，trp基因表达会受到抑制，而如果在色氨酸缺乏的培养基中或在γ干扰素存在的情况下生长，trp基因表达会被诱导。此外，当在色氨酸前体吲哚存在的情况下培养感染细胞时，编码功能性色氨酸合成酶的菌株中trp基因的表达会受到抑制。用真核蛋白质合成抑制剂环己酰亚胺进行的实验结果表明，除了细胞内色氨酸池的绝对大小外，宿主对可用色氨酸的竞争在调节trp基因表达中起关键作用。色氨酸类似物5-氟色氨酸抑制trp基因表达并诱导沙眼衣原体异常生物体的形成。5-氟色氨酸的生长抑制特性可用外源性色氨酸逆转，但不能用吲哚逆转。总体而言，我们的结果表明，根据色氨酸可用性调节trp基因表达的能力对该生物体的细胞内存活有利。此外，沙眼衣原体保留了对色氨酸限制作出反应的能力这一事实支持了以下观点，即γ干扰素的体内抗衣原体作用是通过诱导色氨酸降解酶吲哚胺2,3-双加氧酶实现的。
