Bacterial nucleoside catabolism controls quorum sensing and commensal-to-pathogen transition in the Drosophila gut

Although gut microbiomes are generally symbiotic or commensal, some of microbiomes become pathogenic under certain circumstances, which is one of key processes of pathogenesis. However, the factors involved in these complex gut-microbe interactions are largely unknown. Here we show that bacterial nucleoside catabolism using gut luminal uridine is required to boost inter-bacterial communications and gut pathogenesis in Drosophila. We found that uridine-derived uracil is required for DUOX-dependent ROS generation on the host side, whereas uridine-derived ribose induces quorum sensing and virulence gene expression on the bacterial side. Importantly, genetic ablation of bacterial nucleoside catabolism is sufficient to block the commensal-to-pathogen transition in vivo. Furthermore, we found that major commensal bacteria lack functional nucleoside catabolism, which is required to achieve gut-microbe symbiosis. The discovery of a novel role of bacterial nucleoside catabolism will greatly help to better understand the molecular mechanism of the commensal-to-pathogen transition in different contexts of host-microbe interactions. Overall design: mRNA expression profiles of wild type (Ecc15) and nucleoside hydrolase mutant (Ecc15_delNH) E. carotovora carotovora15 strain were examined by Illumina Hi-seq 2500.尽管肠道微生物组通常以共生（symbiotic）或共栖（commensal）的方式存在，但部分微生物组在特定条件下会转变为致病型，这是致病过程的关键环节之一。然而，介导这类复杂肠道微生物互作的相关因子在很大程度上仍未明确。 本研究证实，利用肠道腔内尿苷的细菌核苷分解代谢，可增强果蝇（Drosophila）体内的细菌间通讯与肠道致病过程。 研究发现，宿主侧依赖双氧化酶（DUOX）的活性氧（Reactive Oxygen Species, ROS）生成需要尿苷衍生的尿嘧啶；而细菌侧的尿苷衍生核糖则可诱导群体感应（quorum sensing）与毒力基因的表达。 尤为重要的是，在体内通过基因敲除抑制细菌的核苷分解代谢，足以阻断共栖向致病型的转变过程。 此外，研究发现主要的共栖细菌缺乏功能性核苷分解代谢途径，而这一途径正是实现肠道微生物共生所必需的。 本研究揭示了细菌核苷分解代谢的全新功能，将有助于我们更深入地理解宿主-微生物互作不同场景下共栖向致病型转变的分子机制。 实验设计：采用Illumina Hi-seq 2500测序平台，对野生型胡萝卜软腐欧文氏菌胡萝卜亚种15（E. carotovora carotovora15，缩写Ecc15）及其核苷水解酶突变株（Ecc15_delNH）的mRNA表达谱进行检测分析。