Coordination of host and endosymbiont gene expression governs endosymbiont growth and elimination in the cereal weevil Sitophilus spp. DOI Creative Commons
Mariana Galvão Ferrarini,

Agnès Vallier,

Carole Vincent-Monégat

et al.

Microbiome, Journal Year: 2023, Volume and Issue: 11(1)

Published: Dec. 13, 2023

Abstract Background Insects living in nutritionally poor environments often establish long-term relationships with intracellular bacteria that supplement their diets and improve adaptive invasive powers. Even though these symbiotic associations have been extensively studied on physiological, ecological, evolutionary levels, few studies focused the molecular dialogue between host endosymbionts to identify genes pathways involved endosymbiosis control dynamics throughout development. Results We simultaneously analyzed endosymbiont gene expression during life cycle of cereal weevil Sitophilus oryzae , from larval stages adults, a particular emphasis emerging adults where Sodalis pierantonius experiences contrasted growth-climax-elimination dynamics. unraveled constant arms race which different biological functions are intertwined coregulated across both partners. These include immunity, metabolism, metal control, apoptosis, bacterial stress response. Conclusions The study tightly regulated functions, at center regulations, provides evidence how hosts finely tune respond physiological challenges constrained by insect development limited ecological niche. Graphical

Language: Английский

Cell death checkpoints in the TNF pathway DOI Open Access
Jon Huyghe, Dario Priem, Mathieu J.M. Bertrand

et al.

Trends in Immunology, Journal Year: 2023, Volume and Issue: 44(8), P. 628 - 643

Published: June 24, 2023

Language: Английский

Citations

61
Targeting the Ubiquitin–Proteasome System and Recent Advances in Cancer Therapy DOI Creative Commons
Daniela Spano, Giuliana Catara

Cells, Journal Year: 2023, Volume and Issue: 13(1), P. 29 - 29

Published: Dec. 22, 2023

Ubiquitination is a reversible post-translational modification based on the chemical addition of ubiquitin to proteins with regulatory effects various signaling pathways. can alter molecular functions tagged substrates respect protein turnover, biological activity, subcellular localization or protein–protein interaction. As result, wide variety cellular processes are under ubiquitination-mediated control, contributing maintenance homeostasis. It follows that dysregulation ubiquitination reactions plays relevant role in pathogenic states human diseases such as neurodegenerative diseases, immune-related pathologies and cancer. In recent decades, enzymes ubiquitin–proteasome system (UPS), including E3 ligases deubiquitinases (DUBs), have attracted attention novel druggable targets for development new anticancer therapeutic approaches. This perspective article summarizes peculiarities shared by involved reaction which, when deregulated, lead tumorigenesis. Accordingly, an overview main pharmacological interventions targeting UPS clinical use still trials provided, also highlighting limitations efficacy these Therefore, attempts circumvent drug resistance side well UPS-related emerging technologies therapeutics discussed.

Language: Английский

Citations

29
A eukaryotic-like ubiquitination system in bacterial antiviral defence DOI
Lydia R. Chambers, Qiaozhen Ye, Jiaxi Cai

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8022), P. 843 - 849

Published: July 17, 2024

Language: Английский

Citations

9
Brucella suis S2 strain inhibits IRE1/caspase-12/caspase-3 pathway-mediated apoptosis of microglia HMC3 by affecting the ubiquitination of CALR DOI Creative Commons
Zhao Wang,

Yanbai Wang,

Shu‐Long Yang

et al.

mSphere, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

ABSTRACT Neurobrucellosis represents a severe complication of brucellosis, posing considerable risk to human health and quality life. This condition arises from an increased susceptibility chronic Brucella infection, significant clinical challenge. One key factor contributing neurobrucellosis is the regulation microglial apoptosis by ; however, exact molecular mechanisms remain largely unresolved. In this study, clone 3 (HMC3) cells were infected with suis vaccine strain S2 ( B. S2) at varying multiplicity infection (MOI) durations assess its effects on IRE1/caspase-12/caspase-3 signaling pathway. Following suppression pathway S2, calreticulin (CALR) was identified through ubiquitin-modified proteomics (data accessible via ProteomeXchange, identifier PXD056006). To further investigate, CALR-overexpression knockdown HMC3 cell lines elucidate mechanism which inhibits in cells. conclusion, our findings demonstrate that suppresses modulating CALR ubiquitination. study provides theoretical basis for exploring offers insights into treatment. IMPORTANCE impacting central nervous system (CNS) due neurological deficits caused , primary features including meningitis, encephalitis, brain abscesses, demyelinating lesions. These nonspecific symptoms often lead misdiagnosis or delayed diagnosis, increasing recurrent infections. Consequently, persistent relapse are critical challenges management neurobrucellosis, closely linked ’s survival replication within microglia. Interestingly, may inhibit microglia mitigating endoplasmic reticulum (ER) stress, though precise unexplored. Thus, will specific provide deeper pathogenesis treatment neurobrucellosis.

Language: Английский

Citations

1
Specificities and redundancies in the NEL family of bacterial E3 ubiquitin ligases of Salmonella enterica serovar Typhimurium DOI Creative Commons
Andrea Bullones-Bolaños,

Paula Martín-Muñoz,

Claudia Vallejo-Grijalba

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 1, 2024

Salmonella enterica serovar Typhimurium expresses two type III secretion systems, T3SS1 and T3SS2, which are encoded in pathogenicity island 1 (SPI1) SPI2, respectively. These essential virulent factors that secrete more than 40 effectors translocated into host animal cells. This study focuses on three of these effectors, SlrP, SspH1, SspH2, members the NEL family E3 ubiquitin ligases. We compared their expression, regulation, translocation patterns, role cell invasion intracellular proliferation, ability to interact ubiquitinate specific partners, effect cytokine secretion. found transcription genes encoding depends virulence regulator PhoP. Although have potential be secreted through SspH1 SspH2 is largely restricted T3SS2 due expression pattern. detected a for proliferation inside fibroblasts masked by redundancy. The generation chimeric proteins allowed us demonstrate N-terminal part proteins, containing leucine-rich repeat motifs, confers specificity towards ubiquitination targets. Furthermore, polyubiquitination patterns generated were different each effector, with Lys48 linkages being predominant SspH2. Finally, our experiments support an anti-inflammatory

Language: Английский

Citations

5
The acetylase activity of Cdu1 regulates bacterial exit from infected cells by protecting Chlamydia effectors from degradation DOI Creative Commons
Robert J. Bastidas, Mateusz Kędzior,

Robert K. Davidson

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: Feb. 15, 2024

Many cellular processes are regulated by ubiquitin-mediated proteasomal degradation. Pathogens can regulate eukaryotic proteolysis through the delivery of proteins with de-ubiquitinating (DUB) activities. The obligate intracellular pathogen Chlamydia trachomatis secretes Cdu1 (ChlaDUB1), a dual deubiquitinase and Lys-acetyltransferase, that promotes Golgi remodeling survival infected host cells presumably regulating ubiquitination bacterial proteins. Here, we determined Cdu1’s acetylase but not its DUB activity is important to protect from We further identified three C. on pathogen-containing vacuole (InaC, IpaM, CTL0480) required Cdu1‘s for protection degradation these Cdu1-protected optimal egress cells. These findings highlight non-canonical mechanism pathogen-mediated virulence factors after their into coordinated regulation secreted effector

Language: Английский

Citations

5
Opportunistic Infections, Mortality Risk, and Prevention Strategies in Patients With Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome DOI Creative Commons
Mary M. Czech, Jennifer Cuéllar-Rodríguez, Bhavisha A. Patel

et al.

Open Forum Infectious Diseases, Journal Year: 2024, Volume and Issue: 11(7)

Published: June 28, 2024

Abstract Background VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a genetic disorder characterized by bone marrow failure and systemic inflammation, putting patients at risk for infections. This study comprehensively examines the prevalence of opportunistic infections in with VEXAS, evaluating their impact on clinical outcomes potential preventive measures. Methods Patients confirmed were included. Survival analysis logistic regression used to identify associations between mortality. Infection rates (IRs) Pneumocystis jirovecii pneumonia (PJP) alphaherpesviruses calculated over prospective 8-month observation period relationship prophylaxis. Results Of 94 6% developed PJP; 15% had alphaherpesvirus reactivation, varicella zoster virus (VZV) being most common herpesvirus; 10% contracted nontuberculous mycobacterial (NTM) infection. Risk death was significantly increased per month following diagnosis PJP (hazard ratio [HR], 72.41 [95% confidence interval {CI}, 13.67–533.70]) or NTM (HR, 29.09 CI, 9.51–88.79]). Increased odds also observed history herpes simplex (HSV) reactivation (odds [OR], 12.10 1.29–114.80]) but not VZV (OR, 0.89 .30–2.59]). Prophylaxis (IR, 0.001 vs 0 person-day, P < .01) 0.006 = .04) markedly decreased infection number needed treat 4 7, respectively. Conclusions Opportunistic are VEXAS. who develop PJP, HSV, death. against highly effective.

Language: Английский

Citations

5
Ubiquitin: A double-edged sword in hepatitis B virus-induced hepatocellular carcinoma DOI
Arpita Kar, Sandipan Mukherjee, Soumyadeep Mukherjee

et al.

Virology, Journal Year: 2024, Volume and Issue: 599, P. 110199 - 110199

Published: Aug. 7, 2024

Language: Английский

Citations

5
The NEL Family of Bacterial E3 Ubiquitin Ligases DOI Open Access
Andrea Bullones-Bolaños, Joaquín Bernal-Bayard, Francisco Ramos‐Morales

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7725 - 7725

Published: July 13, 2022

Some pathogenic or symbiotic Gram-negative bacteria can manipulate the ubiquitination system of eukaryotic host cell using a variety strategies. Members genera Salmonella, Shigella, Sinorhizobium, and Ralstonia, among others, express E3 ubiquitin ligases that belong to NEL family. These use type III secretion systems translocate these proteins into cells, where they will find their targets. In this review, we first introduce process consider various ways alter ligation machinery. We then focus on members family, expression, translocation, subcellular localization in cell, review what is known about structure proteins, function virulence symbiosis, specific

Language: Английский

Citations

23
Exploitation of the Host Ubiquitin System: Means by Legionella pneumophila DOI Creative Commons
Jingjing Luo, Lidong Wang, Lei Song

et al.

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 22, 2021

Ubiquitination is a commonly used post-translational modification (PTM) in eukaryotic cells, which regulates wide variety of cellular processes, such as differentiation, apoptosis, cell cycle, and immunity. Because its essential role immunity, the ubiquitin network common target infectious agents, have evolved various effective strategies to hijack co-opt signaling for their benefit. The intracellular pathogen Legionella pneumophila represents one example; it utilizes large cohort virulence factors called effectors modulate diverse resulting formation compartment Legionella-containing vacuole (LCV) that supports replication. Many these function re-orchestrate with distinct biochemical activities. In this review, we highlight recent progress mechanism action L. involved ubiquitination discuss roles bacterial host biology.

Language: Английский

Citations

27