Control of the Escherichia coli Sialoregulon by Transcriptional Repressor NanR
Control of the Escherichia coli Sialoregulon by Transcriptional Repressor NanR
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DOI：
10.1128/jb.00692-13
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发表时间：
2013-10-01
影响因子：
3.2
通讯作者：
Vimr, Eric R.
中科院分区：
文献类型：
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作者：
Kalivoda, Kathryn A.;Steenbergen, Susan M.;Vimr, Eric R.
NanR是> 8，500个GntR超家族螺旋-转角-螺旋转录调节因子之一，控制大肠杆菌中唾液酸催化所需基因的表达。预计在携带nanR直系同源物的相关细菌中也是如此。唾液酸是主要在动物谱系中发现的超过40种天然存在的九碳酮糖酸的家族，所述动物谱系包括后口动物谱系中的海星至人类。唾液酸在发育、免疫、蛋白质定位和稳定性以及体内平衡中起作用。它们还作为微生物碳源和氮源以及宿主定殖期间细胞识别的配体。微生物唾液酸代谢对宿主-微生物相互作用的重要性使其成为治疗开发的靶点。利用这一目标取决于了解唾液酸代谢途径在广泛的进化不同的细菌。在这里，我们通过转录组，遗传和生物化学分析表明，最常见的唾液酸，N-乙酰神经氨酸，诱导nanATEK-yhcH，yjhATS（nanCMS），和yjhBC操纵子直接灭活NanR，主要是二聚体形式的阻遏物转化为约30 kDa的无活性单体。此外，其他结果分别鉴定了调节子和操纵子中的关键氨基酸残基和核苷酸。综合结果更好地定义了唾液酸如何通过NanR作用，影响一组重要的宿主衍生代谢物的代谢通量。因此，E.大肠杆菌作为一个有价值的模型，了解唾液酸代谢途径的细菌。
NanR, one of >8,500 GntR superfamily helix-turn-helix transcriptional regulators, controls expression of the genes required for catabolism of sialic acids in Escherichia coli. It is predicted to do the same in related bacteria harboring orthologs of nanR. The sialic acids are a family of over 40 naturally occurring nine-carbon keto-sugar acids found mainly in the animal lineage, which includes starfish to humans in the deuterostome lineage. Sialic acids function in development, immunity, protein localization and stability, and homeostasis. They also serve as microbial carbon and nitrogen sources and ligands for cell recognition during host colonization. The importance of microbial sialic acid metabolism for host-microbe interactions has made it a target for therapeutic development. Exploiting this target depends on understanding sialometabolic pathways in a wide range of evolutionarily distinct bacteria. Here, we show by transcriptome, genetic, and biochemical analyses that the most common sialic acid, N-acetylneuraminate, induces the nanATEK-yhcH, yjhATS (nanCMS), and yjhBC operons by directly inactivating NanR, converting the predominantly dimeric form of the repressor to an inactive monomer of approximately 30-kDa. Additionally, other results identify critical amino acid residues and nucleotides in the regulator and operator, respectively. The combined results better define how sialic acids, acting through NanR, affect the metabolic flux of an important group of host-derived metabolites. Thus, E. coli serves as a valuable model for understanding sialocatabolic pathways in bacteria.