ADP heptose, a novel pathogen‐associated molecular pattern identified in Helicobacter pylori. Issue 8 (21st June 2019)

• Record Type: Journal Article
• Authors: Pfannkuch, Lennart; Hurwitz, Robert; Trauisen, Jan; Sigulla, Janine; Poeschke, Marcella; Matzner, Laura; Kosma, Paul; Schmid, Monika; Meyer, Thomas F.
• Is Part Of: FASEB journal. Volume 33:Issue 8(2019)
• Page Start: 9087
• Page End: 9099
• Publication Date: 2019-06-21
• Subjects: NF‐κB -- ALPK1 -- TIFA -- LPS -- PAMP; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201802555R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: The gastric pathogen Helicobacter pylori activates the NF‐κB pathway in human epithelial cells via 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 H. pylori revealed surprisingly low amounts, failing to explain NF‐κB activation. Instead, we identified ADP ‐glycero‐ β‐D‐ manno‐ heptose (ADP heptose), a derivative of HBP, as the predominant PAMP in lysates of H. pylori 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 H. pylori –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 Helicobacter pylori . FASEB J. 33, 9087–9099 (2019). www.fasebj.org