Brucella effectors NyxA and NyxB target SENP3 to modulate the subcellular localisation of nucleolar proteins

• Published in: Nature communications Vol. 14; no. 1; p. 102
• Main Authors: Louche, Arthur, Blanco, Amandine, Lacerda, Thais Lourdes Santos, Cancade-Veyre, Lison, Lionnet, Claire, Bergé, Célia, Rolando, Monica, Lembo, Frédérique, Borg, Jean-Paul, Buchrieser, Carmen, Nagahama, Masami, Gérard, Francine C. A., Gorvel, Jean-Pierre, Gueguen-Chaignon, Virginie, Terradot, Laurent, Salcedo, Suzana P.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.01.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 14; 14/19; 14/34; 14/35; 14/63; 631/326/41/2180; 631/326/41/2536; 631/326/421; 631/326/88; 82/80; Accumulation; Autophagy; Bacteria; Biosynthesis; Brucella; Brucella abortus; Brucella abortus - metabolism; Brucellosis - microbiology; Cell Nucleolus - metabolism; Cell Nucleus - metabolism; Crystal structure; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Effectors; Humanities and Social Sciences; Humans; Immune response; Intracellular; Intracellular signalling; Life Sciences; Localization; Molecular Chaperones - metabolism; multidisciplinary; Nuclear Proteins - metabolism; Nucleoli; Pathogens; Protease; Protein Inhibitors of Activated STAT - metabolism; Proteinase; Proteins; Replication; Science; Science (multidisciplinary); Sequestering; Signal transduction; Ubiquitin-protein ligase
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35763-8

The cell nucleus is a primary target for intracellular bacterial pathogens to counteract immune responses and hijack host signalling pathways to cause disease. Here we identify two Brucella abortus effectors, NyxA and NyxB, that interfere with host protease SENP3, and this facilitates intracellular replication of the pathogen. The translocated Nyx effectors directly interact with SENP3 via a defined acidic patch (identified from the crystal structure of NyxB), preventing nucleolar localisation of SENP3 at late stages of infection. By sequestering SENP3, the effectors promote cytoplasmic accumulation of nucleolar AAA-ATPase NVL and ribosomal protein L5 (RPL5) in effector-enriched structures in the vicinity of replicating bacteria. The shuttling of ribosomal biogenesis-associated nucleolar proteins is inhibited by SENP3 and requires the autophagy-initiation protein Beclin1 and the SUMO-E3 ligase PIAS3. Our results highlight a nucleomodulatory function of two Brucella effectors and reveal that SENP3 is a crucial regulator of the subcellular localisation of nucleolar proteins during Brucella infection, promoting intracellular replication of the pathogen. The bacterium Brucella abortus is an intracellular pathogen that modulates autophagy in host cells. Here, the authors identify two B. abortus effectors that interact with host protease SENP3, thus promoting cytoplasmic accumulation of nucleolar proteins associated with ribosomal biogenesis and facilitating intracellular replication of the pathogen