2026-10-11T05:54:13Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33814014 2026-09-15T17:54:46Z category_4 category_8 category_12 category_14 category_39 category_106 category_46 category_61 category_64 category_122 category_132 portal_5 item_type_3 month_year_09_2026

<p>Strains and plasmids used in this study.</p> Tian Tian He (24377284) Pu Yu Tang (24377275) Qian Ru Zhao (7521626) Jie Zhang (64655) Pin Nie (183956) Hong Bing Yu (10320566) Hai Xia Xie (24377287) Biochemistry Microbiology Cell Biology Molecular Biology Ecology Science Policy Immunology Developmental Biology Cancer Mental Health Infectious Diseases separate functional domains maintains elevated levels finding may reveal underlying mechanisms remain g ., il promoting tak1 phosphorylation inhibiting tak1 abrogates driving tak1 phosphorylation esej also interacts dependent inflammatory responses edwardsiella piscicida </ κb signaling pathway esej orchestrates nf dependent mechanisms edwardsiella </ κb pathway piscicida </ inflammatory cytokines dependent k27 vivo </ κb signaling κb cascade κb activation upon infection two ubiquitin transcriptional activity terminal region t3ss ). subsequent degradation subsequent activation provide evidence linked polyubiquitination interaction increases increased transcription important pathogen essential role conserved effector central domain 6 ). <div><p><i>Edwardsiella piscicida</i> PPD130/91 is an important pathogen that infects both fish and humans. Upon infection, <i>E. piscicida</i> induces strong inflammatory responses through its type III secretion system (T3SS). The underlying mechanisms remain to be defined. Here, we demonstrate that <i>E. piscicida</i> T3SS effector EseJ activates the NF-κB pathway in macrophages, leading to increased transcription and secretion of multiple pro-inflammatory cytokines (e.g., IL-1β and IL-6). EseJ orchestrates NF-κB signaling by interfering with two ubiquitin-dependent mechanisms that are mediated by separate functional domains of EseJ. EseJ binds to the NF-κB subunit p65 via its N-terminal region of amino acids 1–242, preventing the K48-linked polyubiquitination of p65 and its subsequent degradation by the proteasome. This maintains elevated levels of total and phosphorylated p65 (p-p65), facilitating p65 nuclear translocation and enhancing its transcriptional activity. EseJ also interacts with TAK1 and TRAF6 (both are upstream of the NF-κB signaling pathway) via its central domain (aa 243–532), thereby promoting the formation of a stable TRAF6-TAK1 complex. This interaction increases the TRAF6-dependent K27-linked polyubiquitination of TAK1, driving TAK1 phosphorylation and the subsequent activation of the IKK-IκB-NF-κB cascade. Inhibiting TAK1 abrogates this signaling, confirming the essential role of TAK1 in EseJ-induced NF-κB activation. <i>In vivo</i> studies using zebrafish larvae also demonstrated that EseJ is required for <i>E. piscicida</i> to induce the production of pro-inflammatory cytokines. Together, we provide evidence that EseJ targets both TAK1 and p65 to promote NF-κB-dependent inflammatory responses. Given the similarities among EseJ homologues in other bacteria, our finding may reveal a conserved effector-mediated immune signaling across diverse Gram-negative pathogens.</p></div> 2026-09-15T17:54:32Z Dataset Dataset 10.1371/journal.ppat.1014260.t001 https://figshare.com/articles/dataset/_p_Strains_and_plasmids_used_in_this_study_p_/33814014 CC BY 4.0