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

The E3 ubiquitin ligase RNF115 regulates phagosome maturation and host response to bacterial infection DOI Creative Commons
Orsolya Bilkei‐Gorzo, Tiaan Heunis, José Luis Marín‐Rubio

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(23)

Published: Oct. 25, 2022

Abstract Phagocytosis is a key process in innate immunity and homeostasis. After particle uptake, newly formed phagosomes mature by acquisition of endolysosomal enzymes. Macrophage activation interferon gamma (IFN‐γ) increases microbicidal activity, but delays phagosomal maturation an unknown mechanism. Using quantitative proteomics, we show that proteins harbour high levels typical atypical ubiquitin chain types. Moreover, ubiquitylation vesicle trafficking substantially enhanced upon IFN‐γ macrophages, suggesting role regulating functions. We identified the E3 ligase RNF115, which enriched on activated as important regulator maturation. Loss RNF115 protein or activity increased cytokine responses to bacterial infection, both immune signalling from phagosome phagolysosomal are controlled through ubiquitylation. knock‐out mice less tissue damage response S. aureus indicating inflammatory vivo . In conclusion, regulators functions during infections.

Language: Английский

Citations

18
Dysregulation of deubiquitinylases: a linchpin of gastrointestinal diseases DOI Creative Commons

Lorena Ferino,

Michael Naumann

Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Selective Autophagy Mediated by Protein Ubiquitination in Major Prevalent Zoonoses DOI Creative Commons

Chi Meng,

Fengyuan Jiao,

Gengxu Zhou

et al.

Transboundary and Emerging Diseases, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Zoonotic diseases not only cause great harm to animal health but also involve the development of husbandry, which in turn endangers human life and public safety. Protein ubiquitination autophagy are important ways for body degrade invading pathogens, correspond ubiquitin (Ub)‐proteasome system (UPS) autophagic lysosomal pathway (ALP), respectively, play an role occurrence diseases. For UPS, substrate is delivered 26S proteasome via a cascade subsequently degraded removed. ALP, encapsulated form autophagosomes, fuse with lysosomes autophagolysosomes, eventually cleared. However, variety zoonotic pathogens can interfere protein process promote self‐replication survival, resist host immune defense. This article reviews mechanisms by multiple degradation pathways, providing new perspective treatment prevention

Language: Английский

Citations

0
The Role of Bacterial Proteases From the Microbiome in Human Disease DOI Creative Commons
Ying‐Chiang J. Lee

Cellular Microbiology, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Proteases degrade proteins and peptides, recycling materials preventing unnecessary buildup within the cell. They can also be secreted act in extracellular space. Bacterial proteases are often function as virulence factors. In context of microbiome, they contribute to host–microbe interactions facilitate colonization disease pathogenesis. Thus, proteolytic activity is found upregulated patient cohorts. this minireview, we describe how bacterial microbiome display various bioactivities such disruption barrier function, degradation host defense compounds, modulating inflammatory responses, allowing for microbial movement. We focus on gut, skin, vaginal, urinary microbiomes specific organisms have activities that exacerbate or lead human diseases.

Language: Английский

Citations

0
Structural diversity and oligomerization of bacterial ubiquitin-like proteins DOI

Minheng Gong,

Qiaozhen Ye, Yajie Gu

et al.

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

Published: April 1, 2025

Language: Английский

Citations

0
Huib32: A Potent and Selective USP32 Inhibitor Modulating Endosomal Processes and Advancing Cell-Permeable USP32 Probes DOI Creative Commons
Stephan Scherpe,

Vito Pol,

Raymond Kooij

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

ABSTRACT Deubiquitinating enzymes (DUBs) are pivotal regulators of ubiquitination, a vital post-translational modification essential for cellular processes. Dysregulated DUB activity disrupts homeostasis, driving diseases like cancer and neurodegeneration. Ubiquitin-specific protease 32 (USP32) has emerged as promising therapeutic target due to its role in endosomal autophagosomal dynamics association with breast, ovarian, lung cancers. Here, we describe Huib32 ( H uman de U biquitinase Inhi b itor 32) USP32 inhibitor. Cyanimide-containing potently selectively inhibits by covalently binding the active site Cys743 vitro cells, enhancing substrate altering morphology, mimicking depletion. Additionally, present two activity-based probes (ABPs), Huib32*1 Huib32*2 , which enable precise detection confirm probe selectivity via mass spectrometry. Together, represent unique approach targeting USP32, offering new research tools potential avenues disorders involving endocytic trafficking.

Language: Английский

Citations

0
CSP ubiquitylation favours Plasmodium berghei survival during early liver stage infection DOI Creative Commons
Susana Baptista, Aparajita Lahree, Sofia Marques

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 25, 2025

The circumsporozoite protein (CSP), an essential that covers the surface of Plasmodium sporozoite, is a key player in multiple stages parasite development within mosquito and during interactions between sporozoites mammalian hepatocytes. Here, we identify novel function berghei CSP: preventing elimination early hepatic infection, through its ubiquitylation at two lysine (K) residues, K252 K258, located C-terminal domain. A transgenic line lacking these residues exhibited significant decrease infectivity, with parasites being eliminated 4 h after infection. reduced infectivity correlated increased association host autophagy markers, LC3 LAMP1, to parasitophorous vacuole membrane liver stage parasite. Notably, inhibiting pathway fully rescued mutant from elimination. Collectively, reveal strategy employed by evade clearance which relies on specific CSP results via autophagic lysosomal activity.

Language: Английский

Citations

0
Molecular biology of autoinflammatory diseases DOI Creative Commons
Junya Masumoto, Wei Zhou,

Shinnosuke Morikawa

et al.

Inflammation and Regeneration, Journal Year: 2021, Volume and Issue: 41(1)

Published: Oct. 11, 2021

The long battle between humans and various physical, chemical, biological insults that cause cell injury (e.g., products of tissue damage, metabolites, and/or infections) have led to the evolution adaptive responses. These responses are triggered by recognition damage-associated molecular patterns (DAMPs) pathogen-associated (PAMPs), usually cells innate immune system. DAMPs PAMPs recognized pattern receptors (PRRs) expressed cells; this triggers inflammation. Autoinflammatory diseases strongly associated with dysregulation PRR interactomes, which include inflammasomes, NF-κB-activating signalosomes, type I interferon-inducing immuno-proteasome; disruptions regulation these interactomes leads inflammasomopathies, relopathies, interferonopathies, proteasome-associated autoinflammatory syndromes, respectively. In review, we discuss currently accepted mechanisms underlying several diseases.

Language: Английский

Citations

21
Diaphorina citri E3 ubiquitin ligase RNF115 inhibits CLas bacterial proliferation by targeting to the host histone H1 DOI Open Access

Xiao‐Jin Zou,

Yihong Zhang, Can Zhang

et al.

Insect Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract The Asian citrus psyllid (ACP), Diaphorina citri , serves as the primary vector for Candidatus Liberibacter asiaticus ( C Las), pathogen responsible Huanglongbing (HLB). D. modulates expression of its key proteins in response to Las infection. Previous research has revealed that infection significantly alters levels E3 ubiquitin ligases ; however, specific functions these remain largely uncharacterized. In this study, a total 11 were identified from proteomics database among which ligase RNF115 was upregulated following RING finger protein 115 (RNF115) consists 156 amino acids and contains domain at N‐terminus. Silencing via RNA interference (RNAi) injecting inhibitor disulfiram, targets RNF115, increased bacterial content . contrast, injection recombinant markedly inhibited proliferation. Furthermore, interaction between histone H1 confirmed using yeast 2‐hybrid assay, pull‐down experiments molecular docking analysis. Knockdown RNAi reduced content, whereas led an increase within These findings suggest may induce upregulation leading subsequent interactions with facilitate ubiquitination H1, ultimately resulting inhibiting proliferation

Language: Английский

Citations

0
Computational Based Designing of a Multi-Epitopes Vaccine against Burkholderia mallei DOI Creative Commons
Muhammad Irfan, Saifullah Khan,

Alaa R. Hameed

et al.

Vaccines, Journal Year: 2022, Volume and Issue: 10(10), P. 1580 - 1580

Published: Sept. 21, 2022

The emergence of antibiotic resistance in bacterial species is a major threat to public health and has resulted high mortality as well care costs. Burkholderia mallei one the etiological agents care-associated infections. As no licensed vaccine available against pathogen herein, using reverse vaccinology, bioinformatics, immunoinformatics approaches, multi-epitope-based B. was designed. In completely sequenced proteomes mallei, 18,405 core, 3671 non-redundant, 14,734 redundant proteins were predicted. Among non-redundant proteins, 3 predicted extracellular matrix, 11 outer membrane periplasmic membrane. Only two type VI secretion system tube protein (Hcp) IV pilus secretin selected for epitope prediction. Six epitopes, EAMPERMPAA, RSSPPAAGA, DNRPISINL, RQRFDAHAR, AERERQRFDA, HARAAQLEPL, shortlisted multi-epitopes design. epitopes linked each other via specific GPGPG linker peptide then an adjuvant molecule through EAAAK make designed more immunologically potent. also found have favorable physicochemical properties with low molecular weight fewer transmembrane helices. Molecular docking studies revealed construct stable binding MHC-I, MHC-II, TLR-4 energy scores -944.1 kcal/mol, -975.5 -1067.3 respectively. dynamic simulation assay noticed dynamics docked vaccine-receptors complexes drastic changes observed. Binding free energies estimation net value -283.74 kcal/mol vaccine-MHC-I complex, -296.88 vaccine-MHC-II -586.38 vaccine-TLR-4 complex. These findings validate that showed promising ability terms immune receptors may be capable eliciting strong responses once administered host. Further evidence from experimentations mice models required real protection mallei.

Language: Английский

Citations

13