Biomedical research institute
     
    You are here: Home / Institute / News / ADP-heptose, a bacterial sugar that induces inflammation

    ADP-heptose, a bacterial sugar that induces inflammation

    •  
    A study diriged by Cécile Arrieumerlou

    During an infection, our cells are able to detect the presence of pathogens

    through the interactions between pathogen-associated molecular patterns (PAMPs) and Pathogen Recognition Receptors (PRRs). These interactions trigger complex signaling mechanisms that quickly activate an inflammatory response and help fight off the infection. The team of Cécile Arrieumerlou, in collaboration with the “Laboratoire de Chimie des Biomolécules” of Laurence Mulard at Institut Pasteur, has identified ADP-heptose as a new bacterial PAMP. They found  that this small bacterial sugar, which is present in the vast majority of Gram negative bacteria, is able to trigger an inflammatory response involving the atypical kinase ALPK1 and the protein TIFA. This work was published in EMBO Reports in December 2018.

     

    ADP-heptose is a newly identified PAMP of Shigella flexneri

    During an infection, the detection of pathogens is mediated through the interactions between pathogen-associated molecular patterns (PAMPs) and pathogen recognition receptors (PRRs). β-Heptose 1,7-bisphosphate (βHBP), a soluble metabolite of the lipopolysaccharide (LPS) synthesis pathway was recently described as a bacterial PAMP. It was reported that βHBP sensing leads to the oligomerization of TIFA proteins, a mechanism controlling the activation of the transcription factor NF-κB and the expression of pro-inflammatory genes. In this work, the teams headed by Cécile Arrieumerlou and Laurence Mulard compare the ability of chemically synthesized βHBP and Shigella flexneri lysate to induce inflammatory signaling in human epithelial cells. They show that, unlike bacterial lysate, βHBP fails to initiate rapid oligomerization of TIFA proteins. βHBP only induces delayed signaling, suggesting that this molecule has to be processed intracellularly to trigger inflammation and that, it is therefore not a PAMP. Instead, they identify ADP-heptose, another soluble intermediate of the LPS pathway, as the bacterial PAMP responsible for rapid TIFA oligomerization, and show that its cellular detection occurs down to 10-10 M. Finally, they show that during S. flexneri infection, ADP-heptose sensing triggers cytokine production, a process that sequentially depends on the atypical kinase ALPK1 and the protein TIFA.

     

    This study rules out a direct contribution of βHBP in the control of inflammation, and identifies ADP-heptose as a key bacterial immuno-modulatory molecule during S. flexneri infection. Given that this bacterial sugar is present in the vast majority of Gram negative bacteria, this work opens new perspectives to better understand the complexity of the molecular interactions that occur during bacterial infections or control intestinal homeostasis.

     

     

     

    Learn more

    García-Weber, D.*, Dangeard, AS.*, Cornil, J., Thai, L., Rytter, H., Zamyatina, A., Mulard, L.A., Arrieumerlou, C. (2018). ADP-heptose is a newly identified pathogen associated molecular pattern of Shigella flexneri infection. EMBO Rep. 10.15252/embr.201846943

     

    Researcher contact:

     

    Copyright © Creative Commons Attribution 4.0 Unported Licence (CC BY)