Antimicrobial resistance of Pseudomonas aeruginosa: navigating clinical impacts, current resistance trends, and innovations in breaking therapies

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

Published: April 5, 2024

Pseudomonas aeruginosa , a Gram-negative bacterium, is recognized for its adaptability and opportunistic nature. It poses substantial challenge in clinical settings due to complicated antibiotic resistance mechanisms, biofilm formation, capacity persistent infections both animal human hosts. Recent studies revealed potential zoonotic transmission of P. between animals, the environment, populations which highlights awareness this microbe. Implementation One Health approach, underscores connection human, animal, environmental health, we aim offer comprehensive perspective on current landscape management. This review presents innovative strategies designed counteract infections. Traditional antibiotics, while effective many cases, are increasingly compromised by development multidrug-resistant strains. Non-antibiotic avenues, such as quorum sensing inhibition, phage therapy, nanoparticle-based treatments, emerging promising alternatives. However, their application encounters obstacles like cost, side effects, safety concerns. Effectively addressing necessitates research efforts, advancements development, comprehension host-pathogen interactions deal with resilient pathogen.

Language: Английский

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Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review

Biomedicines, Journal Year: 2024, Volume and Issue: 12(7), P. 1467 - 1467

Published: July 2, 2024

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families the human genome, which CYP1, CYP2, and CYP3 are prominent. Beyond drug CYP metabolize endogenous compounds such as lipids, proteins, hormones to maintain physiological homeostasis. Thus, dysregulation CYP450 can lead different endocrine disorders. Moreover, significantly contribute fatty acid cholesterol synthesis, bile biosynthesis, impacting cellular physiology disease pathogenesis. Their diverse functions emphasize their therapeutic potential managing hypercholesterolemia neurodegenerative diseases. Additionally, implicated onset development illnesses cancer, influencing chemotherapy outcomes. Assessment enzyme expression activity aids evaluating liver health state differentiating between diseases, guiding decisions, optimizing efficacy. Understanding roles clinical effect genetic polymorphisms crucial for developing personalized strategies enhancing responses patient populations.

Language: Английский

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Transcriptional Regulators Controlling Virulence in Pseudomonas aeruginosa

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 11895 - 11895

Published: July 25, 2023

Pseudomonas aeruginosa is a pathogen capable of colonizing virtually every human tissue. The host colonization competence and versatility this are powered by wide array virulence factors necessary in different steps the infection process. This includes involved bacterial motility attachment, biofilm formation, production secretion extracellular invasive enzymes exotoxins, toxic secondary metabolites, acquisition iron. Expression these during tightly regulated, which allows their only when they needed. process optimizes virulence. In work, we review intricate network transcriptional regulators that control expression P. aeruginosa, including one- two-component systems σ factors. Because inhibition holds promise as target for new antimicrobials, blocking trigger determinants promising strategy to fight clinically relevant pathogen.

Language: Английский

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Molecular mechanism of siderophore regulation by the Pseudomonas aeruginosa BfmRS two-component system in response to osmotic stress

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: March 9, 2024

Abstract Pseudomonas aeruginosa , a common nosocomial pathogen, relies on siderophores to acquire iron, crucial for its survival in various environments and during host infections. However, understanding the molecular mechanisms of siderophore regulation remains incomplete. In this study, we found that BfmRS two-component system, previously associated with biofilm formation quorum sensing, is essential under high osmolality stress. Activated BfmR directly bound promoter regions pvd, fpv femARI gene clusters, thereby activating their transcription promoting production. Subsequent proteomic phenotypic analyses confirmed deletion reduces siderophore-related proteins impairs bacterial iron-deficient conditions. Furthermore, phylogenetic analysis demonstrated conservation system across species, functional evidences also indicated homologues from putida KT2440 sp. MRSN12121 could bind key genes osmolality-mediated increases production were observed. This work illuminates novel signaling pathway enhances our siderophore-mediated interactions community establishment.

Language: Английский

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Pseudomonas aeruginosa two-component system CprRS regulates HigBA expression and bacterial cytotoxicity in response to LL-37 stress

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(1), P. e1011946 - e1011946

Published: Jan. 10, 2024

Pseudomonas aeruginosa is a highly pathogenic bacterium known for its ability to sense and coordinate the production of virulence factors in response host immune responses. However, regulatory mechanisms underlying this process have remained largely elusive. In study, we investigate two-component system CprRS P. unveil crucial role sensor protein CprS sensing human defense peptide LL-37, thereby modulating bacterial virulence. We demonstrate that acts as phosphatase presence leading phosphorylation activation regulator CprR. The results prove CprR directly recognizes specific sequence within promoter region HigBA toxin-antitoxin system, resulting enhanced expression toxin HigB. Importantly, LL-37-induced HigB promotes type III secretion effectors, reduced proinflammatory cytokines increased cytotoxicity towards macrophages. Moreover, mutations cprS or cprR significantly impair survival both macrophage insect infection models. This study uncovers mechanism enabling detect respond innate responses while maintaining balanced gene profile. Additionally, provides new evidence insights into complex T3SS environment, contributing better understanding host-microbe communication development novel strategies combat infections.

Language: Английский

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Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infection

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(12), P. 3284 - 3303

Published: Oct. 25, 2024

Language: Английский

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Host–Microbe Interactions in Healthy and CSOM-Affected Middle Ears

Microorganisms, Journal Year: 2025, Volume and Issue: 13(2), P. 339 - 339

Published: Feb. 5, 2025

Chronic suppurative otitis media (CSOM) is a chronic middle ear inflammatory condition due to persistent polymicrobial infection. The interaction between local immune responses and microbial communities not well understood, complicating the development of targeted therapies. This study aimed characterise cell composition in CSOM-affected mucosa, focusing on Pseudomonas aeruginosa Staphylococcus aureus. A total 24 CSOM patients 22 controls undergoing tympanomastoid surgery participated this prospective study. Middle mastoid mucosa were collected for histological microbiological analysis. Bacterial identification was performed using standard culture methods Vitek MS, while populations quantified via immunohistochemistry. Statistical analyses Kruskal–Wallis Mann–Whitney tests. Microbiology results identified multiple pathogens CSOM, including S. aureus P. aeruginosa, with infections 10 samples. exhibited significantly elevated cells, CD3+, CD20+, CD68+ compared controls. Histological analysis showed Gram-positive bacteria three samples, positive antibody staining (20.8%) (12.5%) patients. Controls had no bacterial staining. Intracellular may evade host defences reduce antibiotic efficacy, contributing persistence. Targeting intracellular future treatments, along studying communities, could improve management strategies.

Language: Английский

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Cellulophaga algicola alginate lyase and Pseudomonas aeruginosa Psl glycoside hydrolase inhibit biofilm formation by Pseudomonas aeruginosa CF2843 on three-dimensional aggregates of lung epithelial cells

Biofilm, Journal Year: 2025, Volume and Issue: 9, P. 100265 - 100265

Published: Feb. 22, 2025

Pseudomonas aeruginosa is an opportunistic pathogen that produces a biofilm containing the polysaccharides, alginate, Psl, and Pel, causes chronic lung infection in cystic fibrosis patients. Others we have previously explored use of alginate lyases inhibiting P. formation on plastic epithelial cell monolayers. We now employ more physiologically representative model system, i.e., three-dimensional aggregates A549 cells cultured under conditions microgravity rotary culture system to mimic natural environment, isolated clinical strain, CF2843 engineered by transposon-mediated integration express Green Fluorescent Protein for which also report complete genome sequence. Immunostaining lectin binding studies indicated harbored sialylated fucosylated epitopes as well Muc1, Muc5Ac, β-catenin their surfaces, suggestive mucin secretion presence tight junctions, hallmark features tissue. Using this validated with confocal microscopy viable bacterial counts readouts, demonstrated Cellulophaga algicola lyase Psl glycoside hydrolase, but not Pel inhibit aggregates.

Language: Английский

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Diversification of Pseudomonas aeruginosa After Inhaled Tobramycin Therapy of Cystic Fibrosis Patients: Genotypic and Phenotypic Characteristics of Paired Pre- and Post-Treatment Isolates

Microorganisms, Journal Year: 2025, Volume and Issue: 13(4), P. 730 - 730

Published: March 24, 2025

This study examines the impact of inhaled tobramycin therapy on within-host changes in P. aeruginosa strains isolated from Bulgarian patients with CF prior to and post treatment. Genotypic comparison by RAPD-PCR indicated that most pre-treatment isolates had a high similarity were genetically comparatively close other countries known increased morbidity or treatment requirements. Most post-treatment were, however, distant their counterparts, showing genotypic diversification after Phenotypic comparisons showed lower ODmax reached during groswth an lag-time isolates. All capable invasion intracellular reproduction within A549 cultured cells. The addition sub-inhibitory amounts (1/4 1/2 MIC) growth higher relative fitness (as percentage untreated control) strains. effects sub-MICs biofilm did not show such pronounced trend. However, when resazurin-based viability test was applied, advantage confirmed for both broth cultures. In spite that, according determined MIC values, all tobramycin-sensitive, data this imply development tolerance antibiotic survived

Language: Английский

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Bacterial metallothionein, PmtA, a novel stress protein found on the bacterial surface of Pseudomonas aeruginosa and involved in management of oxidative stress and phagocytosis

mSphere, Journal Year: 2024, Volume and Issue: 9(5)

Published: May 7, 2024

Metallothioneins (MTs) are small cysteine-rich proteins that play important roles in homeostasis and protection against heavy metal toxicity oxidative stress. The opportunistic pathogen,

Language: Английский

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