Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin, Germany.
Department of Infectious Diseases and Pulmonary Medicine, Charité, University Hospital Berlin, Berlin, Germany.
FASEB J. 2019 Aug;33(8):9087-9099. doi: 10.1096/fj.201802555R. Epub 2019 Jun 21.
The gastric pathogen activates the NF-κB pathway in human epithelial cells the recently discovered α-kinase 1 TRAF-interacting protein with forkhead-associated domain (TIFA) axis. We and others showed that this pathway can be triggered by heptose 1,7-bisphosphate (HBP), an LPS intermediate produced in gram-negative bacteria that represents a new pathogen-associated molecular pattern (PAMP). Here, we report that our attempts to identify HBP in lysates of revealed surprisingly low amounts, failing to explain NF-κB activation. Instead, we identified ADP--β-D--heptose (ADP heptose), a derivative of HBP, as the predominant PAMP in lysates of and other gram-negative bacteria. ADP heptose exhibits significantly higher activity than HBP, and cells specifically sensed the presence of the β-form, even when the compound was added extracellularly. The data lead us to conclude that ADP heptose not only constitutes the key PAMP responsible for -induced NF-κB activation in epithelial cells, but it acts as a general gram-negative bacterial PAMP.-Pfannkuch, L., Hurwitz, R., Traulsen, J., Sigulla, J., Poeschke, M., Matzner, L., Kosma, P., Schmid, M., Meyer, T. F. ADP heptose, a novel pathogen-associated molecular pattern identified in .
胃病原体通过新近发现的与 TRAF 相互作用的α-激酶 1 衔接蛋白（TIFA）轴激活人上皮细胞中的 NF-κB 途径。我们和其他人表明，该途径可以被庚糖 1,7-双磷酸（HBP）触发，HBP 是革兰氏阴性菌中产生的 LPS 中间体，代表了一种新的病原体相关分子模式（PAMP）。在这里，我们报告说，我们试图在 的裂解物中鉴定 HBP，但令人惊讶的是，含量非常低，无法解释 NF-κB 的激活。相反，我们鉴定出 ADP-β-D-庚糖（ADP 庚糖），一种 HBP 的衍生物，是 和其他革兰氏阴性菌裂解物中的主要 PAMP。ADP 庚糖的活性明显高于 HBP，即使化合物在细胞外添加，细胞也能特异性地感知到β-形式的存在。这些数据使我们得出结论，ADP 庚糖不仅构成了负责诱导上皮细胞中 NF-κB 激活的关键 PAMP，而且它还是一种通用的革兰氏阴性细菌 PAMP。-Pfannkuch, L., Hurwitz, R., Traulsen, J., Sigulla, J., Poeschke, M., Matzner, L., Kosma, P., Schmid, M., Meyer, T. F. ADP heptose, a novel pathogen-associated molecular pattern identified in.
