Inhibiting NLRP3 enhances cellular autophagy induced by outer membrane vesicles from Pseudomonas aeruginosa

Microbiology Spectrum, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

ABSTRACT The bacterium Pseudomonas aeruginosa is able to invade lung epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, currently unclear how OMVs from P. (PA-OMVs) affect their impact on oxidative stress, autophagy, other physiological activities of cells. In study, we found that PA-OMVs activated stress autophagy in We demonstrated the NLRP3 (NLR family, pyrin domain containing 3) inhibitor MCC950 can enhance induced by PA-OMVs. main function related body’s immune response inflammation regulation. most common NLRP3. Additionally, showed not only enhanced expression AMP-activated protein kinase, a key regulator cellular energy homeostasis, reactive oxygen species, which play crucial role signaling but also significantly Inhibiting further process autophagy. These results demonstrate activate both inflammasome, with suppressing certain extent, hoping provide broad ideas for future applications IMPORTANCE discovery exposed induce protective immunity significant. Specifically, addition an inhibitor, MCC950, has been decrease targets while simultaneously enhancing activity This finding unveils novel theoretical framework development vaccines, highlighting new anti-infective responses. By elucidating mechanisms through trigger bolster defenses, research opens avenues innovative vaccine design strategies aimed at combatting infections effectively.

Language: Английский

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Bacterial nanotechnology as a paradigm in targeted cancer therapeutic delivery and immunotherapy

Microsystems & Nanoengineering, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 20, 2024

Cancer, a multifaceted and diverse ailment, presents formidable obstacles to traditional treatment modalities. Nanotechnology novel prospects for surmounting these challenges through its capacity facilitate meticulous regulated administration of therapeutic agents malignant cells while concurrently modulating the immune system combat neoplasms. Bacteria their derivatives have emerged as highly versatile multifunctional platforms cancer nanotherapy within realm nanomaterials. This comprehensive review delves into groundbreaking implementations bacterial nanotechnology therapy. encompasses four primary facets: utilization bacteria living conveyors medicinal substances, employment components that stimulate system, deployment vectors tools delivering genetic material, development bacteria-derived nano-drugs intelligent nano-medications. Furthermore, we elucidate merits modalities operation pertaining nano-systems, along with synergize other cutting-edge nanotechnologies, such CRISPR-Cas systems. Additionally, offer insightful viewpoints regarding forthcoming trajectories this expanding domain. It is our deduction embodies propitious innovative paradigm in therapy, which has potential provide numerous advantages synergistic effects enhancing outcomes quality life individuals afflicted cancer.

Language: Английский

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Bacterial Outer Membrane Vesicles: Role in Pathogenesis and Host-Cell Interactions

Antibiotics, Journal Year: 2023, Volume and Issue: 13(1), P. 32 - 32

Published: Dec. 28, 2023

Outer membrane vesicles (OMVs) are small, spherical structures released from the outer membranes of Gram-negative bacteria into surrounding environment. Investigations OMVs range their biogenesis and cargo composition to ability transfer virulence factors modulate host immune responses. This emerging understanding has unveiled pivotal role in pathogenicity infectious diseases, shedding light on interactions with cells, contributions inflammation, potential involvement antimicrobial resistance, promising use for development novel treatments therapies. Numerous studies have associated pathogenic exacerbation inflammatory underlining significance mechanisms these find alternatives combating conditions. Additionally, possess act as decoys, absorbing neutralizing antibiotics, which significantly diminishes efficacy a broad spectrum agents. Another subtopic interest is produced by commensal microbiota. These increasingly acknowledged mutualistic functions, influencing host’s physiology Consequently, play crucial maintaining balanced gut microbiota fostering symbiotic relationships that contribute overall health well-being host. comprehensive review aims provide an up-to-date derived bacteria, summarizing current research findings, elucidating multifaceted diverse biological contexts.

Language: Английский

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Gram-negative bacterial sRNAs encapsulated in OMVs: an emerging class of therapeutic targets in diseases

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 30, 2024

Small regulatory RNAs (sRNAs) encapsulated in outer membrane vesicles (OMVs) are critical post-transcriptional regulators of gene expression prokaryotic and eukaryotic organisms. OMVs small spherical structures released by Gram-negative bacteria that serve as important vehicles for intercellular communication can also play an role bacterial virulence host-pathogen interactions. These molecules interact with mRNAs or proteins affect various cellular functions physiological processes the producing bacteria. This review aims to provide insight into current understanding sRNA localization highlights identification, characterization functional implications these sRNAs. By examining research gaps this field, we aim inspire further exploration progress investigating potential therapeutic applications OMV-encapsulated sRNAs diseases.

Language: Английский

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Effects of bacterial extracellular vesicles derived from oral and gastrointestinal pathogens on systemic diseases

Microbiological Research, Journal Year: 2024, Volume and Issue: 285, P. 127788 - 127788

Published: June 1, 2024

Language: Английский

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The role and mechanisms of Helicobacter pylori outer membrane vesicles in the pathogenesis of extra-gastrointestinal diseases

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: 200, P. 107312 - 107312

Published: Jan. 22, 2025

Language: Английский

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Extracellular Vesicles in Periodontitis: Pathogenic Mechanisms and Therapeutic Potential

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 1317 - 1331

Published: Jan. 1, 2025

Periodontitis is a prevalent yet frequently overlooked oral disease that linked to range of systemic conditions. Although basic treatment and periodontal surgery can alleviate the symptoms periodontitis certain extent, severe tissue defects or refractory cases not effective. Extracellular vesicles (EVs) are subcellular lipid bilayer particles come from variety sources in biological fluids vertebrates. They play key role intercellular communication by transporting multiple signaling molecules. Recent research has indicated EVs derived pathogens trigger periodontitis, exacerbate damage, potentially disseminate other parts body, leading Conversely, extracellular dental stem cells (DSCs) have demonstrated ability regulate local immune environment foster regeneration repair tissues, positioning them as promising candidate for cell-free therapeutic approaches periodontitis. This review aims summarize latest on involvement different pathogenesis especially systematically elucidate mechanism secreted periodontitis-related diseases first time. By uncovering these complex regulatory processes, new more effective be explored battle against its associated diseases.

Language: Английский

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Postbiotics and their biotherapeutic potential for chronic disease and their feature perspective: a review

Frontiers in Microbiomes, Journal Year: 2025, Volume and Issue: 4

Published: March 3, 2025

Postbiotics, which are bioactive compounds derived from the metabolic processes of probiotics, gaining recognition as a promising alternative for managing chronic diseases without need live microorganisms, positioning them valuable strategy in biotherapeutics that offers both curative and preventive techniques modern medicine. This paper provides comprehensive review potential health benefits postbiotics, particularly concerning noncommunicable like diabetes, cancer, obesity cardiovascular conditions, present significant global challenges. We explore various mechanisms by postbiotics exert their beneficial effects, including immune modulation to enhance body’s response reduce inflammation, well improving gut barrier function maintain integrity prevent increased intestinal permeability. Additionally, antioxidant properties play critical role neutralizing oxidative stress, is linked progression diseases. Despite encouraging insights into benefits, we highlight urgent further research clarify specific roles different postbiotic components. A deeper understanding these essential developing targeted healthcare applications, advancing this knowledge, aim create innovative strategies could significantly outcomes at-risk populations. Ultimately, integrating interventions has improve care contribute overall well-being affected individuals communities.

Language: Английский

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Multivariate Analysis of Individual Bacterial Outer Membrane Vesicles Using Fluorescence Microscopy

Chemical & Biomedical Imaging, Journal Year: 2024, Volume and Issue: 2(5), P. 352 - 361

Published: April 19, 2024

Gram-negative bacteria produce outer membrane vesicles (OMVs) that play a critical role in cell–cell communication and virulence. OMVs have emerged as promising therapeutic agents for various biological applications such vaccines targeted drug delivery. However, the full potential of is currently constrained by inherent heterogeneities, size cargo differences, traditional ensemble assays are limited their ability to reveal OMV heterogeneity. To overcome this issue, we devised an innovative approach enabling identification characteristics individual OMVs. This method, employing fluorescence microscopy, facilitates detection variations surface markers. demonstrate our utilize oral bacterium Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) which produces with bimodal distribution. As part its virulence, A. secretes leukotoxin (LtxA) two forms: soluble associated We observed correlation between toxin presence where larger were much more likely possess LtxA compared smaller In addition, noted that, among smallest (<100 nm diameter), fractions positive range from 0 30%, while largest (>200 diameter) 70 100% positive.

Language: Английский

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Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

Pathogens and Immunity, Journal Year: 2024, Volume and Issue: 9(1), P. 56 - 90

Published: April 23, 2024

There are a growing number of studies linking the composition human microbiome to disease states and treatment responses, especially in context cancer. This has raised significant interest developing microbes microbial products as cancer immunotherapeutics that mimic or recapitulate beneficial effects host-microbe interactions. Bacterial extracellular vesicles (bEVs) nano-sized, membrane-bound particles secreted by essentially all bacteria species contain diverse bioactive cargo producing cell. They have fundamental role facilitating interactions among cells same species, different even with multicellular host organisms colonization (microbiome) infection. The interaction bEVs immune system been studied extensively infection suggests bEV depend largely on species. thus provide functional diversity, while also being nonreplicative, having inherent cell-targeting qualities, potentially overcoming natural barriers. These characteristics make them highly appealing for development immunotherapeutics. Both natively engineered now investigated their application immunotherapeutics, vaccines, drug delivery vehicles, combinations above, promising early results. both intrinsic immunomodulatory properties ability be modified could harnessed next-generation microbe-inspired therapies. Nonetheless, there remain major outstanding questions regarding how observed preclinical effectiveness will translate from murine models primates, humans particular. Moreover, research into pharmacology, toxicology, mass manufacturing this potential novel therapeutic platform is still at stages. In review, we highlight breadth cells, focusing immunologic main mechanism action currently development. We review literature ongoing efforts develop variety bacterial therapy finally discuss overcome challenges clinical translation.

Language: Английский

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