Two novel regulators of N-acetyl-galactosamine utilization pathway and distinct roles in bacterial infections.
Two novel regulators of N-acetyl-galactosamine utilization pathway and distinct roles in bacterial infections.
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N-乙酰半乳糖胺利用途径的两种新型调节剂及其在细菌感染中的不同作用
DOI：
10.1002/mbo3.307
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发表时间：
2015-12
期刊：
影响因子：
3.4
通讯作者：
Feng Y
中科院分区：
文献类型：
--
作者：
Zhang H;Ravcheev DA;Hu D;Zhang F;Gong X;Hao L;Cao M;Rodionov DA;Wang C;Feng Y
细菌病原体可以利用代谢途径来促进其成功的感染周期，但对d-半乳糖胺（GalN）/N-乙酰基-d-半乳糖胺（GalNAc）催化剂途径在细菌发病机制中的作用知之甚少。在这里，我们报告了链球菌GalN/GalNAc利用途径的基因组重建和多样化的阿加调节子。我们描绘了两个新的旁系同源的AgaR监管机构的GalN/GalNAc catalysts途径。电泳迁移率变动分析实验表明，AgaR 2（AgaR 1）结合预测的回文酶，逆转录定量聚合酶链反应和RNA-seq的组合体内数据表明，AgaR 2（而不是AgaR 1）可以有效地抑制靶基因的转录。从猪链球菌05 ZYH 33中去除agaR 2（而不是agaR 1）显著增强对Hep-2细胞的粘附和对RAW 264.7巨噬细胞的抗吞噬能力。正如预期的那样，AgaR 2介导的S.在小鼠和仔猪的实验模型中，suis削弱了其致病性。我们的发现发现了两个新的监管机构具体的GalN/GalNAc催化剂，并分配到细菌感染的不同角色。据我们所知，它可能代表了第一个范例，连接的GalN/GalNAc catalysts途径的细菌发病机制。
Bacterial pathogens can exploit metabolic pathways to facilitate their successful infection cycles, but little is known about roles of d‐galactosamine (GalN)/N‐acetyl‐d‐galactosamine (GalNAc) catabolism pathway in bacterial pathogenesis. Here, we report the genomic reconstruction of GalN/GalNAc utilization pathway in Streptococci and the diversified aga regulons. We delineated two new paralogous AgaR regulators for the GalN/GalNAc catabolism pathway. The electrophoretic mobility shift assays experiment demonstrated that AgaR2 (AgaR1) binds the predicted palindromes, and the combined in vivo data from reverse transcription quantitative polymerase chain reaction and RNA‐seq suggested that AgaR2 (not AgaR1) can effectively repress the transcription of the target genes. Removal of agaR2 (not agaR1) from Streptococcus suis 05ZYH33 augments significantly the abilities of both adherence to Hep‐2 cells and anti‐phagocytosis against RAW264.7 macrophage. As anticipated, the dysfunction in AgaR2‐mediated regulation of S. suis impairs its pathogenicity in experimental models of both mice and piglets. Our finding discovered two novel regulators specific for GalN/GalNAc catabolism and assigned them distinct roles into bacterial infections. To the best of our knowledge, it might represent a first paradigm that links the GalN/GalNAc catabolism pathway to bacterial pathogenesis.