Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Novartis Institutes for Biomedical Research Inc., Cambridge, MA 02139, USA.
Cell Host Microbe. 2021 Sep 8;29(9):1351-1365.e11. doi: 10.1016/j.chom.2021.07.011. Epub 2021 Aug 16.
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-ribosyltransferases（ADPRTs）已被描述为通过修饰宿主蛋白参与发病机制的毒素。在这里，我们报告说 ADPRTs 不仅局限于病原体，而且广泛存在于人类肠道微生物组中，并且经常与噬菌体元件相关。我们在大量临床分离株集中验证了它们的生化活性，并进一步研究了 Bacteroides 中高度丰富的 ADPRT Bxa。Bxa 在 Bacteroides 中表达、分泌并具有酶活性，可 ADP-ribosylate 非肌肉肌球蛋白 II 蛋白。将 Bxa 添加到上皮细胞中可重塑肌动蛋白细胞骨架并诱导肌苷的分泌。编码 B.stercoris 的 Bxa 可以将肌苷用作碳源，并在无菌和改变的 Schaedler 菌群（ASF）小鼠中比 bxa 缺失菌株定植到肠道的数量明显更多。定植与粪便和组织中肌苷浓度的增加相关。总的来说，我们的结果表明 ADPRTs 在微生物组中大量存在，并作为细菌适应因素发挥作用。
