Department of Microbiology and Molecular Genetics, University of Vermont Larner College of Medicine, Burlington, VT 05405, USA.
Cellular, Molecular and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405, USA.
Microbiology (Reading). 2022 Mar;168(3). doi: 10.1099/mic.0.001145.
Glutamine amidotransferase-1 domain-containing AraC-family transcriptional regulators (GATRs) are present in the genomes of many bacteria, including all species. The involvement of several characterized GATRs in amine-containing compound metabolism has been determined, but the full scope of GATR ligands and regulatory networks are still unknown. Here, we characterize 's detection of the animal-derived amine compound creatine, a compound particularly enriched in muscle and ciliated cells by a creatine-specific GATR, PP_3665, here named CahR (Creatine amidohydrolase Regulator). is necessary for transcription of the gene encoding creatinase () in the presence of creatine and is critical for s ability to utilize creatine as a sole source of nitrogen. The CahR/creatine regulon is small, and an electrophoretic mobility shift assay demonstrates strong and specific CahR binding only at the promoter, supporting the conclusion that much of the regulon is dependent on downstream metabolites. Phylogenetic analysis of orthologues associated with orthologues highlights a strain distribution and organization supporting probable horizontal gene transfer, particularly evident within the genus . This study identifies and characterizes the GATR that transcriptionally controls 's metabolism of creatine, broadening the scope of known GATR ligands and suggesting GATR diversification during evolution of metabolism for aliphatic nitrogen compounds.
谷氨酰胺氨基转移酶-1 结构域包含的 AraC 家族转录调节剂 (GATRs) 存在于许多细菌的基因组中，包括所有物种。已经确定了几种有特征的 GATRs 参与含胺化合物的代谢，但 GATR 配体和调节网络的全貌仍不清楚。在这里，我们描述了 GATR 对动物源性胺化合物肌酸的检测，肌酸是一种特别富含肌肉和纤毛细胞的化合物，由一种肌酸特异性 GATR，即 PP_3665 ，命名为 CahR（肌酸酰胺水解酶调节剂）来调节。在有肌酸存在的情况下，CahR 对于编码肌酸酶（）的基因的转录是必需的，并且对于能够将肌酸作为唯一氮源利用至关重要。CahR/肌酸调控子很小，电泳迁移率变动分析表明，只有在 启动子处，CahR 才能强烈且特异性地结合，这支持了调控子的大部分依赖于下游代谢物的结论。与 同源物相关的 同源物的系统发育分析突出了一种菌株分布和组织，支持可能的水平基因转移，特别是在属内非常明显。本研究鉴定并描述了转录控制 的肌酸代谢的 GATR，拓宽了已知 GATR 配体的范围，并表明在代谢进化过程中 GATR 的多样化。
