ADP-Heptose and Nucleotide Enhancers Drive Fusobacteria-Induced Inflammation

<p>Colonization by <em>Fusobacteria</em> is associated with diverse inflammatory diseases and cancers, but the underlying molecular mechanisms that drive these associations remain elusive. Here I report studies showing that among commensal bacteria, <em>Fusobacteria</em> are uniquely potent activators of nuclear factor kappa B (NF-κB) signaling, a pathway implicated in inflammatory diseases and cancers. I found that <em>Fusobacterium</em> <em>nucleatum</em> secretes pathogen-associated molecular pattern ADP-heptose and ribonucleotides that together, but not individually, strongly induced NF-<em>κ</em>B signaling as well as the expression of inflammation and cancer associated genes. This finding suggests a regulatory role for extracellular nucleotides in ADP-heptose detection, and also provides a potentially key mechanism for <em>Fusobacteria's</em> diverse disease associations. In addition, the results of these studies suggest that inhibiting the accumulation of either metabolite could prove therapeutically useful.<em></em></p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Thesis

Year dc:date.available

2025

Author dc:creator

• Ye, Linzhi

Contributors dc:contributor

• Sean F. Brady

• Fusobacteria
• inflammation
• cancer
• nuclear factor signaling
• ADP-heptose
• ribonucleotides
• Life Sciences

Repository record dc:identifier

https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/831

OAI identifier oai:identifier

oai:digitalcommons.rockefeller.edu:student_theses_and_dissertations-1835