The Role of Host Cell DNA Methylation in the Immune Response to Bacterial Infection

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

Published: July 29, 2021

Host cells undergo complex transcriptional reprogramming upon infection. Epigenetic changes play a key role in the immune response to bacteria, among which DNA modifications that include methylation have received much attention recent years. The extent of is well known regulate gene expression. Whilst historically was considered be stable epigenetic modification, accumulating evidence indicates patterns can altered rapidly exposure changing environments and pathogens. Furthermore, action proteins regulating methylation, particularly methyltransferases ten-eleven translocation methylcytosine dioxygenases, may modulated, at least part, by bacteria. This review discusses principles insights about regulation host during bacterial

Language: Английский

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Nucleolin: a cell portal for viruses, bacteria, and toxins

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(5)

Published: May 1, 2022

Abstract The main localization of nucleolin is the nucleolus, but this protein present in multiple subcellular sites, and it unconventionally secreted. On cell surface, acts as a receptor for various viruses, some bacteria, toxins. Aim review to discuss characteristics that make able act or co-receptor so many different pathogens. important features emerge are its multivalence, role bridge between surface nucleus. Multiple domains, short linear motifs post-translational modifications confer modulate ability interact with nucleic acids, proteins, also carbohydrates lipids. This modular multivalence allows participate types biomolecular condensates move locations, where can kind molecular glue. It moves from nucleus accompany particles reverse direction, into nucleus, which destination several pathogens manipulate their favour.

Language: Английский

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The Legionella pneumophila Dot/Icm type IV secretion system and its effectors

Microbiology, Journal Year: 2022, Volume and Issue: 168(5)

Published: May 23, 2022

To prevail in the interaction with eukaryotic hosts, many bacterial pathogens use protein secretion systems to release virulence factors at host–pathogen interface and/or deliver them directly into host cells. An outstanding example of complexity and sophistication diversity their substrates, effectors, is Defective organelle trafficking/Intracellular multiplication (Dot/Icm) Type IVB system (T4BSS) Legionella pneumophila related species. species are facultative intracellular environmental protozoa opportunistic human respiratory pathogens. The Dot/Icm T4BSS translocates an exceptionally large number more than 300 per L. strain, essential for evasion phagolysosomal degradation exploitation macrophages as replicative niches. Recent technological advancements imaging complexes have provided new insight architecture allowed us propose models transport mechanism. At same time, significant progress has been made assigning functions about a third discovering unprecedented enzymatic activities concepts subversion. In this review, we describe current knowledge workings machinery provide overview to-date characterized effectors

Language: Английский

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Mycoplasma bovis mastitis in dairy cattle

Frontiers in Veterinary Science, Journal Year: 2024, Volume and Issue: 11

Published: March 6, 2024

Mycoplasma bovis has recently been identified increasingly in dairy cows causing huge economic losses to the industry. M. is a causative agent for mastitis, pneumonia, endometritis, endocarditis, arthritis, otitis media, and many other clinical symptoms cattle. However, some infected are asymptomatic or may not shed pathogen weeks years. This characteristic of , along with lack adequate testing identification methods parts world until recently, allowed be largely undetected despite its increased prevalence farms. Due growing levels antimicrobial resistance among wild-type isolates cell walls mycoplasmas that enable them intrinsically resistant beta-lactam antibiotics widely used farms, there no effective treatment mastitis. Similarly, commercially available vaccine The major constraint developing intervention tools limited knowledge virulence factors mechanisms pathogenesis There quick reliable diagnostic high specificity sensitivity . review summary current state factors, pathogenesis, manifestations, diagnosis, control mastitis cows.

Language: Английский

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High-throughput identification of Toxoplasma gondii effector proteins that target host cell transcription

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(10), P. 1748 - 1762.e8

Published: Oct. 1, 2023

Intracellular pathogens and other endosymbionts reprogram host cell transcription to suppress immune responses recalibrate biosynthetic pathways. This reprogramming is critical in determining the outcome of infection or colonization. We combine pooled CRISPR knockout screening with dual host-microbe single-cell RNA sequencing, a method we term perturb-seq, identify molecular mediators these transcriptional interactions. Applying perturb-seq intracellular pathogen Toxoplasma gondii, are able previously uncharacterized effector proteins directly infer their function from transcriptomic data. show that TgGRA59 contributes export parasite into an effector, TgSOS1, necessary for sustained STAT6 signaling thereby evasion persistence. Together, this work demonstrates tool can be broadly adapted interrogate interactions reveal mechanisms evasion.

Language: Английский

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The Coxiella burnetii T4SS effector protein AnkG hijacks the 7SK small nuclear ribonucleoprotein complex for reprogramming host cell transcription

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(2), P. e1010266 - e1010266

Published: Feb. 8, 2022

Inhibition of host cell apoptosis is crucial for survival and replication several intracellular bacterial pathogens. To interfere with apoptotic pathways, some pathogens use specialized secretion systems to inject effector proteins into the cytosol. One these obligate bacterium Coxiella burnetii , etiological agent zoonotic disease Q fever. In this study, we analyzed molecular activity anti-apoptotic T4SS protein AnkG (CBU0781) understand how C . manipulates viability. We demonstrate by co- RNA-immunoprecipitation that binds DExD box RNA helicase 21 (DDX21) as well 7SK small nuclear ribonucleoprotein (7SK snRNP) complex, an important regulator positive transcription elongation factor b (P-TEFb). The co-immunoprecipitation DDX21 probably mediated salt bridges independent AnkG-7SK snRNP binding, vice versa It known facilitates release P-TEFb from complex. Consistent documented function released in Pol II pause release, sequencing experiments confirmed AnkG-mediated transcriptional reprogramming showed expression genes involved apoptosis, trafficking, are influenced AnkG. Importantly, both essential inhibition emphasizing significance interaction both, RNA. line a critical pathogenesis, deletion strain was severely affected its ability inhibit generate replicative -containing vacuole. conclusion, interference regulatory RNAs represent novel mechanism through which modulates transcription, thereby enhancing permissiveness infection.

Language: Английский

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Nuclear warfare: pathogen manipulation of the nuclear pore complex and nuclear functions

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

Published: March 20, 2025

ABSTRACT Viruses and bacteria exploit the nuclear pore complex (NPC) host functions to bypass cellular barriers manipulate essential processes. frequently engage directly with NPC components, such as nucleoporins, enable genome import evade immune defenses. In contrast, bacterial pathogens rely on secreted effector proteins disrupt transport reprogram transcription. These strategies reflect a remarkable evolutionary convergence, both types of targeting promote infection. This minireview explores overlapping unique mechanisms by which hijack nucleus, shedding light their roles in disease potential avenues for therapeutic intervention.

Language: Английский

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Legionella pneumophila—Virulence Factors and the Possibility of Infection in Dental Practice

Microorganisms, Journal Year: 2022, Volume and Issue: 10(2), P. 255 - 255

Published: Jan. 24, 2022

Legionella pneumophila is defined as a bacterium that can cause severe pneumonia. It found in the natural environment and water, often water tanks. be an integral part of biofilms nature, protozoa which it live provide with food protect from harmful influences; therefore, has ability to move into sustainable but uncultured state (VBNC). L. been shown infections dental practices. The most common transmission route aerosol generated office systems, negatively affect patients healthcare professionals. way becoming infected through instruments, unit. In addition these bacteria, team may exposed other bacteria viruses. Therefore, vital regularly maintains decontaminates unit, sterilizes all accessories come it. addition, regular control offices necessary.

Language: Английский

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Orientia tsutsugamushi Nucleomodulin Ank13 Exploits the RaDAR Nuclear Import Pathway To Modulate Host Cell Transcription

mBio, Journal Year: 2021, Volume and Issue: 12(4)

Published: Aug. 3, 2021

Orientia tsutsugamushi is the etiologic agent of scrub typhus, deadliest all diseases caused by obligate intracellular bacteria. Nucleomodulins, bacterial effectors that dysregulate eukaryotic transcription, are being increasingly recognized as key virulence factors. How they translocate into nucleus and their functionally essential domains poorly defined. We demonstrate Ank13, an O. effector conserved among clinical isolates expressed during infection, localizes to in importin β1-independent manner. Rather, Ank13 nucleotropism requires isoleucine at thirteenth position its fourth ankyrin repeat, consistent with utilization RaDAR (RanGDP-ankyrin repeats) nuclear import. RNA-seq analyses cells expressing green fluorescent protein (GFP)-tagged nucleotropism-deficient Ank13I127R, or Ank13ΔF-box, which lacks F-box domain for interacting SCF ubiquitin ligase, revealed be a nucleomodulin predominantly downregulates transcription more than 2,000 genes. Its ability do so involves synergistic mutually exclusive manners. also acts cytoplasm smaller cohorts The effector's toxicity yeast heavily depends on less nucleotropism. Genes negatively regulated include those involved inflammatory response, transcriptional control, epigenetics. Importantly, majority genes GFP-Ank13 most strongly quiescent repressed tsutsugamushi-infected when expression strongest. first identified coopt multifaceted functions via F-box-dependent -independent mechanisms globally reprogram host cell transcription. IMPORTANCE Nucleomodulins recently defined used diverse bacteria manipulate gene convert hospitable niches. nucleomodulins enter nucleus, functional domains, modulate incompletely characterized. pathogen causes can fatal. example microbial coopts It dysregulates multitude control response prominent. does dependent independent both eukaryotic-like interfaces ligase machinery. Nearly downregulated ectopically cells, implicating importance colonization typhus molecular pathogenesis.

Language: Английский

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Bacterial Epigenomics: Coming of Age

mSystems, Journal Year: 2021, Volume and Issue: 6(4)

Published: Aug. 17, 2021

Epigenetic DNA methylation in bacteria has been traditionally studied the context of antiparasitic defense and as part innate immune discrimination between self nonself DNA. However, sequencing advances that allow genome-wide analysis at single-base resolution are nowadays expanding have propelled a modern epigenomic revolution our understanding extent, evolution, physiological significance methylation.

Language: Английский

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