Bacterial ADP-ribosyltransferases (ADPRTs) have been described as toxins involved in pathogenesis through the modification of host proteins. Here, we report that ADPRTs are not pathogen restricted but widely prevalent in the human gut microbiome and often associated with phage elements. We validated their biochemical activity in a large clinical isolate collection and further examined Bxa, a highly abundant ADPRT in Bacteroides. Bxa is expressed, secreted, and enzymatically active in Bacteroides and can ADP-ribosylate non-muscle myosin II proteins. Addition of Bxa to epithelial cells remodeled the actin cytoskeleton and induced secretion of inosine. Bxa-encoding B. stercoris can use inosine as a carbon source and colonizes the gut to significantly greater numbers than a bxa-deleted strain in germ-free and altered Schaedler flora (ASF) mice. Colonization correlated with increased inosine concentrations in the feces and tissues. Altogether, our results show that ADPRTs are abundant in the microbiome and act as bacterial fitness factors.

细菌 ADP-核糖基转移酶 (ADPRT) 已被描述为通过宿主蛋白修饰参与发病机制的毒素。在这里，我们报告说 ADPRT 不受病原体限制，但在人类肠道微生物组中广泛流行，并且通常与噬菌体元素相关。我们在大型临床分离物集合中验证了它们的生化活性，并进一步检查了 Bxa，一种在拟杆菌属中高度丰富的 ADPRT 。Bxa 在拟杆菌中表达、分泌和具有酶活性，并且可以 ADP-核糖基化非肌肉肌球蛋白 II 蛋白。向上皮细胞添加 Bxa 可重塑肌动蛋白细胞骨架并诱导肌苷的分泌。Bxa -编码B. stercoris可以使用肌苷作为碳源，并且在无菌和改变的 Schaedler 菌群 (ASF) 小鼠中比bxa 删除菌株在肠道中定殖的数量显着增加。定植与粪便和组织中肌苷浓度增加相关。总而言之，我们的结果表明 ADPRT 在微生物组中含量丰富，并充当细菌适应因子。