The
            <i>Brucella</i>
            effector BspL targets the ER-associated degradation (ERAD) pathway and delays bacterial egress from infected cells

Luizet, Jean-Baptiste; Raymond, Julie; Lacerda, Thaís Lourdes Santos; Barbieux, Emeline; Kambarev, Stanimir; Bonici, Magali; Lembo, Frédérique; Willemart, Kévin; Borg, Jean-Paul; Celli, Jean; Gérard, Francine C A; Muraille, Eric; Gorvel, Jean‐Pierre; Salcedo, Suzana P.

doi:10.1073/pnas.2105324118

Cited by 10 publications

(8 citation statements)

References 45 publications

(72 reference statements)

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“…Previous work listed a subgroup of Brucella candidate effectors containing this kind of potential lipidation motif 16 . We have recently confirmed that one of these Brucella proteins, BspL, is translocated into host cells during infection 19 . Therefore, we set out to determine if two other B. abortus proteins, encoded by BAB1_0296 (BAB_RS17335) and BAB1_0466 (BAB_RS18145), could be translocated into host cells during infection.…”

Section: Resultsmentioning

confidence: 61%

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

et al. 2023

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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.

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Section: Resultsmentioning

confidence: 61%

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

et al. 2023

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“…This infers a bacterial manipulation of the autophagy machinery for subversion of host clearance and promotion of cell-to-cell spreading [ 38 ]. Likewise, the Brucella effector BspL was recently shown to hijack the ER-associated degradation (ERAD) components and delay the formation of the aBCV, thus allowing the bacteria extra time for extensive intracellular multiplication [ 39 ].…”

Section: Limiting Host Immunity To Establish Chronic Brucel...mentioning

confidence: 99%

Immunosuppressive Mechanisms in Brucellosis in Light of Chronic Bacterial Diseases

2022

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Brucellosis is considered one of the major zoonoses worldwide, constituting a critical livestock and human health concern with a huge socio-economic burden. Brucella genus, its etiologic agent, is composed of intracellular bacteria that have evolved a prodigious ability to elude and shape host immunity to establish chronic infection. Brucella’s intracellular lifestyle and pathogen-associated molecular patterns, such as its specific lipopolysaccharide (LPS), are key factors for hiding and hampering recognition by the immune system. Here, we will review the current knowledge of evading and immunosuppressive mechanisms elicited by Brucella species to persist stealthily in their hosts, such as those triggered by their LPS and cyclic β-1,2-d-glucan or involved in neutrophil and monocyte avoidance, antigen presentation impairment, the modulation of T cell responses and immunometabolism. Attractive strategies exploited by other successful chronic pathogenic bacteria, including Mycobacteria, Salmonella, and Chlamydia, will be also discussed, with a special emphasis on the mechanisms operating in brucellosis, such as granuloma formation, pyroptosis, and manipulation of type I and III IFNs, B cells, innate lymphoid cells, and host lipids. A better understanding of these stratagems is essential to fighting bacterial chronic infections and designing innovative treatments and vaccines.

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“…However, once again, Brucella continues displaying an effector of the T4SS system, BspL, to delay the formation of aBCVs that benefit the optimal intracellular replication before disseminating to other cells. At the same time, BspJ, a nucleomodulin, directly or indirectly regulates host cell apoptosis to complete its intracellular cycle [ 87 , 88 ]. As mentioned, the microenvironment inside these vacuoles has limited nutrients.…”

Section: Brucella Phagocytosis and Intracellular Survivalmentioning

confidence: 99%

Brucella Phagocytosis Mediated by Pathogen-Host Interactions and Their Intracellular Survival

et al. 2022

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The Brucella species is the causative agent of brucellosis in humans and animals. So far, brucellosis has caused considerable economic losses and serious public health threats. Furthermore, Brucella is classified as a category B bioterrorism agent. Although the mortality of brucellosis is low, the pathogens are persistent in mammalian hosts and result in chronic infection. Brucella is a facultative intracellular bacterium; hence, it has to invade different professional and non-professional phagocytes through the host phagocytosis mechanism to establish its lifecycle. The phagocytosis of Brucella into the host cells undergoes several phases including Brucella detection, formation of Brucella-containing vacuoles, and Brucella survival via intracellular growth or being killed by host-specific bactericidal activities. Different host surface receptors contribute effectively to recognize Brucella including non-opsonic receptors (toll-like receptors and scavenger receptor A) or opsonic receptors (Fc receptors and complement system receptors). Brucella lacks classical virulence factors such as exotoxin, spores, cytolysins, exoenzymes, virulence plasmid, and capsules. However, once internalized, Brucella expresses various virulence factors to avoid phagolysosome fusion, bypass harsh environments, and establish a replicative niche. This review provides general and updated information regarding Brucella phagocytosis mediated by pathogen-host interactions and their intracellular survival in host cells.

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The Brucella effector BspL targets the ER-associated degradation (ERAD) pathway and delays bacterial egress from infected cells

Cited by 10 publications

References 45 publications

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

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

Immunosuppressive Mechanisms in Brucellosis in Light of Chronic Bacterial Diseases

Brucella Phagocytosis Mediated by Pathogen-Host Interactions and Their Intracellular Survival

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