A widespread NADase domain links bacterial immunity with human TEP1
- 1Centre International de Recherche en Infectiologie (CIRI), Inserm U1111, Universite Claude Bernard Lyon 1, CNRS UMR5308, Ecole Normale Superieure de Lyon, Unive
Abstract
Recent discoveries on bacterial immunity have revealed that several protein domains involved in anti-phage defense are conserved in eukaryotes, such as SIRim, TIR, PNP and gasdermin. Bacterial immune systems therefore have the potential to illuminate fundamental biological mechanisms throughout the tree of life. Here, we report that DUF4062 domains - which we rename NIR (NADase in bacterial immunity and vault ribonucleoproteins) - function in bacterial immunity against phages. We first identified NIR as an effector of Avs defense proteins, where it depletes cellular NAD+ to block viral infection. We then show that NIR domains are recurrently found as effectors in diverse defense systems. We use this association to uncover Vulcan and Vesta, two defense systems which trigger NAD+ depletion upon sensing distinct viral signals. Remarkably, NIR domains are widespread in eukaryotes where they are embedded in multiple NLR-like proteins. In particular, we identified a NIR domain with conserved NADase activity in the human TEP1 protein, a component of the telomerase complex and vault ribonucleoproteins. Together, these findings reveal an enzymatic activity shared between bacterial immunity and enigmatic eukaryotic machineries.
Related
- A widespread bacterial toxin reveals a deeply divergent DNase family neutralized by diverse immunity proteins.
- Paired sequencing of IgA-bound bacteria reveals widespread associations between adaptive immunity and gut microbiome gene expression.
- Widespread Recruitment of ParA-like NTPases into Prokaryotic Immunity reveals a diversity of anti-selfish element strategies
- From CBASS and Thoeris to Panoptes: Phage sponges and the inversion of bacterial immunity
- Tc17-driven antibody-independent mucosal immunity is critical for protection against extracellular bacterial pneumonia
BibTeX
@misc{mouellic2026widespread,
title = {{A widespread NADase domain links bacterial immunity with human TEP1}},
author = {W. Le Mouellic and V. Borges Cardoso and J. Kulsuptrakul and J. Baltenneck and A. Kanevskaya and L. Etienne and F. Rousset},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.749371},
url = {https://www.biorxiv.org/content/10.64898/2026.09.04.749371v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - A widespread NADase domain links bacterial immunity with human TEP1
AU - W. Le Mouellic
AU - V. Borges Cardoso
AU - J. Kulsuptrakul
AU - J. Baltenneck
AU - A. Kanevskaya
AU - L. Etienne
AU - F. Rousset
PY - 2026
DA - 2026/09/04
PB - bioRxiv
DO - 10.64898/2026.09.04.749371
UR - https://www.biorxiv.org/content/10.64898/2026.09.04.749371v1
AB - Recent discoveries on bacterial immunity have revealed that several protein domains involved in anti-phage defense are conserved in eukaryotes, such as SIRim, TIR, PNP and gasdermin. Bacterial immune systems therefore have the potential to illuminate fundamental biological mechanisms throughout the tree of life. Here, we report that DUF4062 domains - which we rename NIR (NADase in bacterial immunity and vault ribonucleoproteins) - function in bacterial immunity against phages. We first identified NIR as an effector of Avs defense proteins, where it depletes cellular NAD+ to block viral infection. We then show that NIR domains are recurrently found as effectors in diverse defense systems. We use this association to uncover Vulcan and Vesta, two defense systems which trigger NAD+ depletion upon sensing distinct viral signals. Remarkably, NIR domains are widespread in eukaryotes where they are embedded in multiple NLR-like proteins. In particular, we identified a NIR domain with conserved NADase activity in the human TEP1 protein, a component of the telomerase complex and vault ribonucleoproteins. Together, these findings reveal an enzymatic activity shared between bacterial immunity and enigmatic eukaryotic machineries.
ER -