Zeitschriftenartikel: „Nucleomodulins“

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Hanford, Hannah E., Juanita Von Dwingelo und Yousef Abu Kwaik. „Bacterial nucleomodulins: A coevolutionary adaptation to the eukaryotic command center“. PLOS Pathogens 17, Nr. 1 (21.01.2021): e1009184. http://dx.doi.org/10.1371/journal.ppat.1009184.

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Through long-term interactions with their hosts, bacterial pathogens have evolved unique arsenals of effector proteins that interact with specific host targets and reprogram the host cell into a permissive niche for pathogen proliferation. The targeting of effector proteins into the host cell nucleus for modulation of nuclear processes is an emerging theme among bacterial pathogens. These unique pathogen effector proteins have been termed in recent years as “nucleomodulins.” The first nucleomodulins were discovered in the phytopathogensAgrobacteriumandXanthomonas, where their nucleomodulins functioned as eukaryotic transcription factors or integrated themselves into host cell DNA to promote tumor induction, respectively. Numerous nucleomodulins were recently identified in mammalian pathogens. Bacterial nucleomodulins are an emerging family of pathogen effector proteins that evolved to target specific components of the host cell command center through various mechanisms. These mechanisms include: chromatin dynamics, histone modification, DNA methylation, RNA splicing, DNA replication, cell cycle, and cell signaling pathways. Nucleomodulins may induce short- or long-term epigenetic modifications of the host cell. In this extensive review, we discuss the current knowledge of nucleomodulins from plant and mammalian pathogens. While many nucleomodulins are already identified, continued research is instrumental in understanding their mechanisms of action and the role they play during the progression of pathogenesis. The continued study of nucleomodulins will enhance our knowledge of their effects on nuclear chromatin dynamics, protein homeostasis, transcriptional landscapes, and the overall host cell epigenome.

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Bierne, Hélène, und Renaud Pourpre. „Bacterial Factors Targeting the Nucleus: The Growing Family of Nucleomodulins“. Toxins 12, Nr. 4 (31.03.2020): 220. http://dx.doi.org/10.3390/toxins12040220.

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Pathogenic bacteria secrete a variety of proteins that manipulate host cell function by targeting components of the plasma membrane, cytosol, or organelles. In the last decade, several studies identified bacterial factors acting within the nucleus on gene expression or other nuclear processes, which has led to the emergence of a new family of effectors called “nucleomodulins”. In human and animal pathogens, Listeria monocytogenes for Gram-positive bacteria and Anaplasma phagocytophilum, Ehrlichia chaffeensis, Chlamydia trachomatis, Legionella pneumophila, Shigella flexneri, and Escherichia coli for Gram-negative bacteria, have led to pioneering discoveries. In this review, we present these paradigms and detail various mechanisms and core elements (e.g., DNA, histones, epigenetic regulators, transcription or splicing factors, signaling proteins) targeted by nucleomodulins. We particularly focus on nucleomodulins interacting with epifactors, such as LntA of Listeria and ankyrin repeat- or tandem repeat-containing effectors of Rickettsiales, and nucleomodulins from various bacterial species acting as post-translational modification enzymes. The study of bacterial nucleomodulins not only generates important knowledge about the control of host responses by microbes but also creates new tools to decipher the dynamic regulations that occur in the nucleus. This research also has potential applications in the field of biotechnology. Finally, this raises questions about the epigenetic effects of infectious diseases.

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Khan, Abdul Arif, und Zakir Khan. „Bacterial nucleomodulins and cancer: An unresolved enigma“. Translational Oncology 14, Nr. 1 (Januar 2021): 100922. http://dx.doi.org/10.1016/j.tranon.2020.100922.

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Bierne, Hélène, und Pascale Cossart. „When bacteria target the nucleus: the emerging family of nucleomodulins“. Cellular Microbiology 14, Nr. 5 (23.02.2012): 622–33. http://dx.doi.org/10.1111/j.1462-5822.2012.01758.x.

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Denzer, Lea, Horst Schroten und Christian Schwerk. „From Gene to Protein—How Bacterial Virulence Factors Manipulate Host Gene Expression During Infection“. International Journal of Molecular Sciences 21, Nr. 10 (25.05.2020): 3730. http://dx.doi.org/10.3390/ijms21103730.

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Bacteria evolved many strategies to survive and persist within host cells. Secretion of bacterial effectors enables bacteria not only to enter the host cell but also to manipulate host gene expression to circumvent clearance by the host immune response. Some effectors were also shown to evade the nucleus to manipulate epigenetic processes as well as transcription and mRNA procession and are therefore classified as nucleomodulins. Others were shown to interfere downstream with gene expression at the level of mRNA stability, favoring either mRNA stabilization or mRNA degradation, translation or protein stability, including mechanisms of protein activation and degradation. Finally, manipulation of innate immune signaling and nutrient supply creates a replicative niche that enables bacterial intracellular persistence and survival. In this review, we want to highlight the divergent strategies applied by intracellular bacteria to evade host immune responses through subversion of host gene expression via bacterial effectors. Since these virulence proteins mimic host cell enzymes or own novel enzymatic functions, characterizing their properties could help to understand the complex interactions between host and pathogen during infections. Additionally, these insights could propose potential targets for medical therapy.

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Sheshukova, Ekaterina V., Natalia M. Ershova, Fedor A. Lipskerov und Tatiana V. Komarova. „Enhanced Synthesis of Foreign Nuclear Protein Stimulates Viral Reproduction via the Induction of γ-Thionin Expression“. Plants 11, Nr. 12 (07.06.2022): 1530. http://dx.doi.org/10.3390/plants11121530.

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Plants are a promising platform for recombinant protein production. Here we propose a novel approach to increase the level of viral vector-mediated recombinant protein synthesis. This approach is based on the hypothesis that antiviral protection is weakened during the antibacterial cellular response. We suggested that introduced to the cell foreign nuclear localized proteins, including effectors such as bacterial nucleomodulins, can interfere with the import of cellular nuclear proteins and launch antibacterial defense reactions, creating favorable conditions for cytoplasmic virus reproduction. Here, we performed synthesis of an artificial nuclear protein—red fluorescent protein (mRFP) fused with a nuclear localization sequence (NLS)—in plant cells as a mimetic of a bacterial effector. Superproduction of mRFP:NLS induced Nicotiana benthamiana γ-thionin (NbγThio) mRNA accumulation. Both NLS-containing protein synthesis and increased NbγThio expression stimulated reproduction of the viral vector based on the genome of crucifer-infecting tobacco mosaic virus (crTMV) in N. benthamiana leaves. We isolated the NbγThio gene promoter (PrγThio) and showed that PrγThio activity sharply increased in response to massive synthesis of GFP fused with NLS. We conclude that NLS-induced PrγThio activation and increased accumulation of Nbγthio mRNA led to the stimulation of GFP expression from crTMV: GFP vector in the transient expression system.

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Shallberg, Lindsey A., und Christopher A. Hunter. „Long live the king: Toxoplasma gondii nucleomodulin inhibits necroptotic cell death“. Cell Host & Microbe 29, Nr. 7 (Juli 2021): 1165–66. http://dx.doi.org/10.1016/j.chom.2021.06.010.

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Klema, Valerie J., Krishna Mohan Sepuru, Nadia Füllbrunn, Tierra R. Farris, Paige S. Dunphy, Jere W. McBride, Krishna Rajarathnam und Kyung H. Choi. „Ehrlichia chaffeensis TRP120 nucleomodulin binds DNA with disordered tandem repeat domain“. PLOS ONE 13, Nr. 4 (11.04.2018): e0194891. http://dx.doi.org/10.1371/journal.pone.0194891.

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Raheem, Abdul, Doukun Lu, Abdul Karim Khalid, Gang Zhao, Yingjie Fu, Yingyu Chen, Xi Chen et al. „The Identification of a Novel Nucleomodulin MbovP467 of Mycoplasmopsis bovis and Its Potential Contribution in Pathogenesis“. Cells 13, Nr. 7 (29.03.2024): 604. http://dx.doi.org/10.3390/cells13070604.

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Mycoplasmopsis bovis is a causative agent of crucial diseases in both dairy and beef cattle leading to substantial economic losses. However, limited control measures for M. bovis-related diseases exist due to a lack of understanding about the virulence factors of this pathogen, a common challenge in mycoplasma research. Consequently, this study aimed to characterize a novel nucleomodulin as a virulence-related factor of M. bovis. Employing bioinformatic tools, we initially predicted MbovP467 to be a secreted protein with a nuclear localization signal based on SignalP scores and the cNLS (Nuclear Localization Signal) Mapper, respectively. Subsequently, the MbovP467 gene was synthesized and cloned into a pEGFP plasmid with EGFP labeling to obtain a recombinant plasmid (rpEGFP-MbovP467) and then was also cloned in pET-30a with a consideration for an Escherichia coli codon bias and expressed and purified for the production of polyclonal antibodies against the recombinant MbovP467 protein. Confocal microscopy and a Western blotting assay confirmed the nuclear location of MbovP467 in bovine macrophages (BoMacs). RNA-seq data revealed 220 up-regulated and 20 down-regulated genes in the rpEGFP-MbovP467-treated BoMac group compared to the control group (pEGFP). A GO- and KEGG-enrichment analysis identified associations with inflammatory responses, G protein-coupled receptor signaling pathways, nuclear receptor activity, sequence-specific DNA binding, the regulation of cell proliferation, IL-8, apoptotic processes, cell growth and death, the TNF signaling pathway, the NF-κB signaling pathway, pathways in cancer, and protein families of signaling and cellular processes among the differentially expressed up-regulated mRNAs. Further experiments, investigating cell viability and the inflammatory response, demonstrated that MbovP467 reduces BoMac cell viability and induces the mRNA expression of IL-1β, IL-6, IL-8, TNF-α, and apoptosis in BoMac cells. Further, MbovP467 increased the promoter activity of TNF-α. In conclusion, this study identified a new nucleomodulin, MbovP467, for M. bovis, which might have an important role in M. bovis pathogenesis.

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Zhao, Gang, Doukun Lu, Shujuan Wang, Hui Zhang, Xifang Zhu, Zhiyu Hao, Ali Dawood et al. „Novel mycoplasma nucleomodulin MbovP475 decreased cell viability by regulating expression of CRYAB and MCF2L2“. Virulence 13, Nr. 1 (19.09.2022): 1590–613. http://dx.doi.org/10.1080/21505594.2022.2117762.

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Farris, Tierra R., Paige S. Dunphy, Bing Zhu, Clayton E. Kibler und Jere W. McBride. „Ehrlichia chaffeensis TRP32 Is a Nucleomodulin That Directly Regulates Expression of Host Genes Governing Differentiation and Proliferation“. Infection and Immunity 84, Nr. 11 (29.08.2016): 3182–94. http://dx.doi.org/10.1128/iai.00657-16.

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Ehrlichia chaffeensis is an obligately intracellular bacterium that reprograms the mononuclear phagocyte through diverse effector-host interactions to modulate numerous host cell processes, including transcription. In a previous study, we reported that E. chaffeensis TRP32, a type 1 secreted effector, interacts with multiple host nucleus-associated proteins and also autoactivates reporter gene expression in yeast. In this study, we demonstrate that TRP32 is a nucleomodulin that binds host DNA and alters host gene transcription. TRP32 enters the host cell nucleus via a noncanonical translocation mechanism that involves phosphorylation of Y179 located in a C-terminal trityrosine motif. Both genistein and mutation of Y179 inhibited TRP32 nuclear entry. An electromobility shift assay (EMSA) demonstrated TRP32 host DNA binding via its tandem repeat domain. TRP32 DNA-binding and motif preference were further confirmed by supershift assays, as well as competition and mutant probe analyses. Using chromatin immunoprecipitation with next-generation sequencing (ChIP-seq), we determined that TRP32 binds a G-rich motif primarily within ±500 bp of the gene transcription start site. An ontology analysis identified genes involved in processes such as immune cell differentiation, chromatin remodeling, and RNA transcription and processing as primary TRP32 targets. TRP32-bound genes ( n = 1,223) were distributed on all chromosomes and included several global regulators of proliferation and inflammation such as those encoding FOS, JUN, AKT3, and NRAS and noncoding RNA genes microRNA 21 (miRNA 21) and miRNA 142. TRP32 target genes were differentially regulated during infection, the majority of which were repressed, and direct repression/activation of these genes by TRP32 was confirmed in vitro with a cellular luciferase reporter assay.

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Ma, Zhongchen, Xiaoyu Deng, Ruirui Li, Ruirui Hu, Yuhe Miao, Yimei Xu, Wei Zheng et al. „Crosstalk of Brucella abortus nucleomodulin BspG and host DNA replication process/mitochondrial respiratory pathway promote anti-apoptosis and infection“. Veterinary Microbiology 268 (Mai 2022): 109414. http://dx.doi.org/10.1016/j.vetmic.2022.109414.

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Adcox, Haley E., Amanda L. Hatke, Shelby E. Andersen, Sarika Gupta, Nathan B. Otto, Mary M. Weber, Richard T. Marconi und Jason A. Carlyon. „Orientia tsutsugamushi Nucleomodulin Ank13 Exploits the RaDAR Nuclear Import Pathway To Modulate Host Cell Transcription“. mBio 12, Nr. 4 (31.08.2021). http://dx.doi.org/10.1128/mbio.01816-21.

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Nucleomodulins are recently defined effectors used by diverse intracellular bacteria to manipulate eukaryotic gene expression and convert host cells into hospitable niches. How nucleomodulins enter the nucleus, their functional domains, and the genes that they modulate are incompletely characterized. Orientia tsutsugamushi is an intracellular bacterial pathogen that causes scrub typhus, which can be fatal. O. tsutsugamushi Ank13 is the first example of a microbial protein that coopts eukaryotic RaDAR (RanGDP-ankyrin repeats) nuclear import.

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Sheshukova, E., N. Ershova und Y. Dorokhov. „THE NUCLEAR LOCALIZATION SEQUENCE OF A MASSIVELY SYNTHESIZED PROTEIN DRAMATICALLY INCREASES PLANT VIRUS REPRODUCTION“. BIOTECHNOLOGY: STATE OF THE ART AND PERSPECTIVES, 2020, 16–17. http://dx.doi.org/10.37747/2312-640x-2020-18-16-17.

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Superproduction of the foreign proteins containing a nuclear localization signal, for example, bacterial nucleomodulins, in the plant cell induces the accumulation of mRNA of the γ-thionin gene and stimulates the reproduction of plant cytoplasmic viruses.

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Prokop, Andrzej, Edith Gouin, Véronique Villiers, Marie-Anne Nahori, Renaud Vincentelli, Mélodie Duval, Pascale Cossart und Olivier Dussurget. „OrfX, a Nucleomodulin Required for Listeria monocytogenes Virulence“. mBio 8, Nr. 5 (31.10.2017). http://dx.doi.org/10.1128/mbio.01550-17.

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ABSTRACT Listeria monocytogenes is a bacterial pathogen causing severe foodborne infections in humans and animals. Listeria can enter into host cells and survive and multiply therein, due to an arsenal of virulence determinants encoded in different loci on the chromosome. Several key Listeria virulence genes are clustered in Listeria pathogenicity island 1. This important locus also contains orfX (lmo0206), a gene of unknown function. Here, we found that OrfX is a small, secreted protein whose expression is positively regulated by PrfA, the major transcriptional activator of Listeria virulence genes. We provide evidence that OrfX is a virulence factor that dampens the oxidative response of infected macrophages, which contributes to intracellular survival of bacteria. OrfX is targeted to the nucleus and interacts with the regulatory protein RybP. We show that in macrophages, the expression of OrfX decreases the level of RybP, which controls cellular infection. Collectively, these data reveal that Listeria targets RybP and evades macrophage oxidative stress for efficient infection. Altogether, OrfX is after LntA, the second virulence factor acting directly in the nucleus. IMPORTANCE Listeria monocytogenes is a model bacterium that has been successfully used over the last 30 years to refine our understanding of the molecular, cellular, and tissular mechanisms of microbial pathogenesis. The major virulence factors of pathogenic Listeria species are located on a single chromosomal locus. Here, we report that the last gene of this locus encodes a small secreted nucleomodulin, OrfX, that is required for bacterial survival within macrophages and in the infected host. This work demonstrates that the production of OrfX contributes to limiting the host innate immune response by dampening the oxidative response of macrophages. We also identify a target of OrfX, RybP, which is an essential pleiotropic regulatory protein of the cell, and uncover its role in host defense. Our data reinforce the view that the secretion of nucleomodulins is an important strategy used by microbial pathogens to promote infection. IMPORTANCE Listeria monocytogenes is a model bacterium that has been successfully used over the last 30 years to refine our understanding of the molecular, cellular, and tissular mechanisms of microbial pathogenesis. The major virulence factors of pathogenic Listeria species are located on a single chromosomal locus. Here, we report that the last gene of this locus encodes a small secreted nucleomodulin, OrfX, that is required for bacterial survival within macrophages and in the infected host. This work demonstrates that the production of OrfX contributes to limiting the host innate immune response by dampening the oxidative response of macrophages. We also identify a target of OrfX, RybP, which is an essential pleiotropic regulatory protein of the cell, and uncover its role in host defense. Our data reinforce the view that the secretion of nucleomodulins is an important strategy used by microbial pathogens to promote infection.

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Rolando, Monica, Cristina Di Silvestre, Laura Gomez Valero und Carmen Buchrieser. „Bacterial methyltransferases: targeting bacterial genomes to host epigenetics“. microLife, 10.08.2022. http://dx.doi.org/10.1093/femsml/uqac014.

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Abstract Methyltransferase (MTases) enzymes transfer methyl groups particularly on proteins and nucleotides thereby participating in controlling the epigenetic information in both prokaryotes and eukaryotes. The concept of epigenetic regulation by DNA methylation has been extensively described for eukaryotes. However, recent studies have extended this concept to bacteria showing that DNA methylation can also exert epigenetic control on bacterial phenotypes. Indeed, the addition of epigenetic information to nucleotide sequences confers adaptive traits including virulence related characteristics to bacterial cells. In eukaryotes, an additional layer of epigenetic regulation is obtained by post-translational modifications of histone proteins. Interestingly, in the last decades it was shown that bacterial MTases, besides playing an important role in epigenetic regulations at the microbe level, by exerting an epigenetic control on their own gene expression, are also important players in host-microbe interactions. Indeed, secreted nucleomodulins, bacterial effectors that target the nucleus of infected cells, have been shown to directly modify the epigenetic landscape of the host. A sub-class of nucleomodulins encodes methyltransferase activities, targeting both host DNA and histone proteins, leading to important transcriptional changes in the host cell. In this review we will focus on lysine and arginine methyltransferases of bacteria and their hosts. The identification and characterization of these enzymes will help to fight bacterial pathogens as they may emerge as promising targets for the development of novel epigenetic inhibitors in both bacteria and the host cells they infect.

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Lee, Ying‐Chiang J. „Examining the functional space of gut microbiome‐derived peptides“. MicrobiologyOpen 12, Nr. 6 (Dezember 2023). http://dx.doi.org/10.1002/mbo3.1393.

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AbstractThe human gut microbiome contains thousands of small, novel peptides that could play a role in microbe–microbe and host–microbe interactions, contributing to human health and disease. Although these peptides have not yet been systematically characterized, computational tools can be used to elucidate the bioactivities they may have. This article proposes probing the functional space of gut microbiome‐derived peptides (MDPs) using in silico approaches for three bioactivities: antimicrobial, anticancer, and nucleomodulins. Machine learning programs that support peptide and protein queries are provided for each bioactivity. Considering the biases of an activity‐centric approach, activity‐agnostic tools using structural and chemical similarity and target prediction are also described. Gut MDPs represent a vast functional space that can not only contribute to our understanding of microbiome interactions but potentially even serve as a source of life‐changing therapeutics.

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Lebreton, Alice, Viviana Job, Marie Ragon, Alban Le Monnier, Andréa Dessen, Pascale Cossart und Hélène Bierne. „Structural Basis for the Inhibition of the Chromatin Repressor BAHD1 by the Bacterial Nucleomodulin LntA“. mBio 5, Nr. 1 (21.01.2014). http://dx.doi.org/10.1128/mbio.00775-13.

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ABSTRACTThe nucleus has emerged as a key target for nucleomodulins, a family of effectors produced by bacterial pathogens to control host transcription or other nuclear processes. The virulence factor LntA fromListeria monocytogenesstimulates interferon responses during infection by inhibiting BAHD1, a nuclear protein involved in gene silencing by promoting heterochromatin formation. So far, whether the interaction between LntA and BAHD1 is direct and sufficient for inhibiting BAHD1 activity is unknown. Here, we functionally characterized the molecular interface between the two proteinsin vitroand in transfected or infected human cells. Based on the known tridimensional structure of LntA, we identified a dilysine motif (K180/K181) in the elbow region of LntA and a central proline-rich region in BAHD1 as crucial for the direct LntA-BAHD1 interaction. To better understand the role played by the dilysine motif in the functionality of LntA, we solved the crystal structure of a K180D/K181D mutant to a 2.2-Å resolution. This mutant highlights a drastic redistribution of surface charges in the vicinity of a groove, which likely plays a role in nucleomodulin target recognition. Mutation of the strategic dilysine motif also abolished the recruitment of LntA to BAHD1-associated nuclear foci and impaired the LntA-mediated stimulation of interferon responses upon infection. Last, the strict conservation of residues K180 and K181 in LntA sequences from 188L. monocytogenesstrains of different serotypes and origins further supports their functional importance. Together, these results provide structural and functional details about the mechanism of inhibition of an epigenetic factor by a bacterial nucleomodulin.IMPORTANCEPathogens have evolved various strategies to deregulate the expression of host defense genes during infection, such as targeting nuclear proteins. LntA, a secreted virulence factor from the bacteriumListeria monocytogenes, stimulates innate immune responses by inhibiting a chromatin-associated repressor, BAHD1. This study reveals the structural features of LntA required for BAHD1 inhibition. LntA interacts directly with a central domain of BAHD1 via a surface patch of conserved positive charges, located nearby a groove on the elbow region of LntA. By demonstrating that this patch is required for LntA function, we provide a better understanding of the molecular mechanism allowing a bacterial pathogen to control host chromatin compaction and gene expression.

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Bui, Duc-Cuong, Tian Luo und Jere W. McBride. „Type 1 secretion system and effectors in Rickettsiales“. Frontiers in Cellular and Infection Microbiology 13 (15.05.2023). http://dx.doi.org/10.3389/fcimb.2023.1175688.

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Obligate intracellular bacteria in the order Rickettsiales are transmitted by arthropod vectors and cause life-threatening infections in humans and animals. While both type 1 and type 4 secretion systems (T1SS and T4SS) have been identified in this group, the most extensive studies of Rickettsiales T1SS and associated effectors have been performed in Ehrlichia. These studies have uncovered important roles for the T1SS effectors in pathobiology and immunity. To evade innate immune responses and promote intracellular survival, Ehrlichia and other related obligate pathogens secrete multiple T1SS effectors which interact with a diverse network of host targets associated with essential cellular processes. T1SS effectors have multiple functional activities during infection including acting as nucleomodulins and ligand mimetics that activate evolutionarily conserved cellular signaling pathways. In Ehrlichia, an array of newly defined major immunoreactive proteins have been identified that are predicted as T1SS substrates and have conformation-dependent antibody epitopes. These findings highlight the underappreciated and largely uncharacterized roles of T1SS effector proteins in pathobiology and immunity. This review summarizes current knowledge regarding roles of T1SS effectors in Rickettsiales members during infection and explores newly identified immunoreactive proteins as potential T1SS substrates and targets of a protective host immune response.

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Mitra, Shubhajit, Paige S. Dunphy, Seema Das, Bing Zhu, Tian Luo und Jere W. McBride. „Ehrlichia chaffeensisTRP120 Effector Targets and Recruits Host Polycomb Group Proteins for Degradation To Promote Intracellular Infection“. Infection and Immunity 86, Nr. 4 (22.01.2018). http://dx.doi.org/10.1128/iai.00845-17.

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ABSTRACTEhrlichia chaffeensishas a group of well-characterized type I secreted tandem repeat protein (TRP) effectors that have moonlighting capabilities. TRPs modulate various cellular processes, reprogram host gene transcription as nucleomodulins, function as ubiquitin ligases, and directly activate conserved host cell signaling pathways to promoteE. chaffeensisinfection. One TRP-interacting host target is polycomb group ring finger protein 5 (PCGF5), a member of the polycomb group (PcG) protein family and a component of the polycomb repressive complex 1 (PRC1). The current study demonstrates that during early infection, PCGF5 strongly colocalizes with TRP120 in the nucleus and later dramatically redistributes to the ehrlichial vacuole along with other PCGF isoforms. Ectopic expression and immunoprecipitation of TRP120 confirmed the interaction of TRP120 with multiple different PCGF isoforms. At 48 h postinfection, a dramatic redistribution of PCGF isoforms from the nucleus to the ehrlichial vacuole was observed, which also temporally coincided with proteasomal degradation of PCGF isoforms and TRP120 expression on the vacuole. A decrease in PRC1-mediated repressive chromatin mark and an altered transcriptional activity in PRC1-associated Hox genes primarily fromHOXBandHOXCclusters were observed along with the degradation of PCGF isoforms, suggesting disruption of the PRC1 inE. chaffeensis-infected cells. Notably, small interfering RNA (siRNA)-mediated knockdown of PCGF isoforms resulted in significantly increasedE. chaffeensisinfection. This study demonstrates a novel strategy in whichE. chaffeensismanipulates PRC complexes through interactions between TRP120 and PCGF isoforms to promote infection.

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Farris, Tierra R., Bing Zhu, Jennifer Y. Wang und Jere W. McBride. „Ehrlichia chaffeensis TRP32 Nucleomodulin Function and Localization Is Regulated by NEDD4L-Mediated Ubiquitination“. Frontiers in Cellular and Infection Microbiology 7 (11.01.2018). http://dx.doi.org/10.3389/fcimb.2017.00534.

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Byerly, Caitlan D., LaNisha L. Patterson und Jere W. McBride. „Ehrlichia TRP effectors: moonlighting, mimicry and infection“. Pathogens and Disease 79, Nr. 5 (01.05.2021). http://dx.doi.org/10.1093/femspd/ftab026.

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ABSTRACT Intracellular bacteria have evolved various strategies to evade host defense mechanisms. Remarkably, the obligately intracellular bacterium, Ehrlichia chaffeensis, hijacks host cell processes of the mononuclear phagocyte to evade host defenses through mechanisms executed in part by tandem repeat protein (TRP) effectors secreted by the type 1 secretion system. In the past decade, TRP120 has emerged as a model moonlighting effector, acting as a ligand mimetic, nucleomodulin and ubiquitin ligase. These defined functions illuminate the diverse roles TRP120 plays in exploiting and manipulating host cell processes, including cytoskeletal organization, vesicle trafficking, cell signaling, transcriptional regulation, post-translational modifications, autophagy and apoptosis. This review will focus on TRP effectors and their expanding roles in infection and provide perspective on Ehrlichia chaffeensis as an invaluable model organism for understanding infection strategies of obligately intracellular bacteria.

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Ma, Zhongchen, Shuifa Yu, Kejian Cheng, Yuhe Miao, Yimei Xu, Ruirui Hu, Wei Zheng et al. „Nucleomodulin BspJ as an effector promotes the colonization of Brucella abortus in the host“. Journal of Veterinary Science 23, Nr. 1 (2022). http://dx.doi.org/10.4142/jvs.21224.

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Ma, Zhongchen, Shuifa Yu, Kejian Cheng, Yuhe Miao, Yimei Xu, Ruirui Hu, Wei Zheng et al. „Nucleomodulin BspJ as an effector promotes the colonization of Brucella abortus in the host“. Journal of Veterinary Science 22 (2021). http://dx.doi.org/10.4142/jvs.2021.22.e94.

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Ma, Zhongchen, Ruirui Li, Ruirui Hu, Xiaoyu Deng, Yimei Xu, Wei Zheng, Jihai Yi, Yong Wang und Chuangfu Chen. „Brucella abortus BspJ Is a Nucleomodulin That Inhibits Macrophage Apoptosis and Promotes Intracellular Survival of Brucella“. Frontiers in Microbiology 11 (12.11.2020). http://dx.doi.org/10.3389/fmicb.2020.599205.

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Pourpre, Renaud, Goran Lakisic, Emma Desgranges, Pascale Cossart, Alessandro Pagliuso und Hélène Bierne. „A bacterial virulence factor interacts with the splicing factor RBM5 and stimulates formation of nuclear RBM5 granules“. Scientific Reports 12, Nr. 1 (19.12.2022). http://dx.doi.org/10.1038/s41598-022-26037-w.

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AbstractL. monocytogenes causes listeriosis, a foodborne disease that is particularly dangerous for immunocompromised individuals and fetuses. Several virulence factors of this bacterial pathogen belong to a family of leucine-rich repeat (LRR)-containing proteins called internalins. Among these, InlP is known for its role in placental infection. We report here a function of InlP in mammalian cell nucleus organization. We demonstrate that bacteria do not produce InlP under in vitro culture conditions. When ectopically expressed in human cells, InlP translocates into the nucleus and changes the morphology of nuclear speckles, which are membrane-less organelles storing splicing factors. Using yeast two-hybrid screen, immunoprecipitation and pull-down experiments, we identify the tumor suppressor and splicing factor RBM5 as a major nuclear target of InlP. InlP inhibits RBM5-induced cell death and stimulate the formation of RBM5-induced nuclear granules, where the SC35 speckle protein redistributes. Taken together, these results suggest that InlP acts as a nucleomodulin controlling compartmentalization and function of RBM5 in the nucleus and that L. monocytogenes has developed a mechanism to target the host cell splicing machinery.

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