Listeria promotes systemic infection by targeting the host deubiquitinase CYLD
Abstract
Listeria monocytogenes (Lm) is an intracellular pathogen that can cause life-threatening systemic infections. Internalin C (InlC) is a secreted factor required for full Lm virulence in systemic models of infection by mechanisms that remain unclear. Here, we show that InlC binds to CYLD, a host deubiquitinase and regulator of innate immunity. Structurally, we reveal the LRR domain of InlC binds the CAP-Gly2 domain of CYLD, independently of InlC's binding site for other host target proteins. Lm strains harboring amino acid substitutions in InlC that selectively disrupt binding to CYLD were examined. We demonstrate that after Lm accesses the host cytosol, InlC recruits CYLD to ubiquitin-positive bacteria. Recruitment of CYLD was dependent on the host E3 ligase RNF213, a major initiator of ubiquitin-mediated defenses. Furthermore, InlC-CYLD binding contributed to Lm virulence in mice. Together, these findings reveal how a secreted bacterial factor promotes the recruitment of a host deubiquitinase to cytosolic bacteria in response to ubiquitin-mediated defenses.
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BibTeX
@article{ammendolia2026listeria,
title = {{Listeria promotes systemic infection by targeting the host deubiquitinase CYLD}},
author = {Dustin Ammendolia and Cara Ellison and Yuelin Zheng and Etienne Coyaud and Estelle M.N. Laurent and Bing-Ru Yan and Bri Manning and Anna Waldmann and Joel Tan and Scott Frendo-Cumbo and Carina Lyons and Ji-Young Youn and Brian Raught and Keith Ireton and Darren Higgins and Paul Elliott and John Brumell},
journal = {Nature Communications},
year = {2026},
month = aug,
doi = {10.1038/s41467-026-77063-5},
url = {https://hal.science/hal-05790858v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Listeria promotes systemic infection by targeting the host deubiquitinase CYLD
AU - Dustin Ammendolia
AU - Cara Ellison
AU - Yuelin Zheng
AU - Etienne Coyaud
AU - Estelle M.N. Laurent
AU - Bing-Ru Yan
AU - Bri Manning
AU - Anna Waldmann
AU - Joel Tan
AU - Scott Frendo-Cumbo
AU - Carina Lyons
AU - Ji-Young Youn
AU - Brian Raught
AU - Keith Ireton
AU - Darren Higgins
AU - Paul Elliott
AU - John Brumell
PY - 2026
DA - 2026/08/31
JO - Nature Communications
DO - 10.1038/s41467-026-77063-5
UR - https://hal.science/hal-05790858v1
AB - Listeria monocytogenes (Lm) is an intracellular pathogen that can cause life-threatening systemic infections. Internalin C (InlC) is a secreted factor required for full Lm virulence in systemic models of infection by mechanisms that remain unclear. Here, we show that InlC binds to CYLD, a host deubiquitinase and regulator of innate immunity. Structurally, we reveal the LRR domain of InlC binds the CAP-Gly2 domain of CYLD, independently of InlC's binding site for other host target proteins. Lm strains harboring amino acid substitutions in InlC that selectively disrupt binding to CYLD were examined. We demonstrate that after Lm accesses the host cytosol, InlC recruits CYLD to ubiquitin-positive bacteria. Recruitment of CYLD was dependent on the host E3 ligase RNF213, a major initiator of ubiquitin-mediated defenses. Furthermore, InlC-CYLD binding contributed to Lm virulence in mice. Together, these findings reveal how a secreted bacterial factor promotes the recruitment of a host deubiquitinase to cytosolic bacteria in response to ubiquitin-mediated defenses.
SN - 2041-1723
SN - 2041-1723
ER -