Role of Efflux Pumps on Antimicrobial Resistance in Pseudomonas aeruginosa

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(24), P. 15779 - 15779

Published: Dec. 13, 2022

Antimicrobial resistance is an old and silent pandemic. Resistant organisms emerge in parallel with new antibiotics, leading to a major global public health crisis over time. Antibiotic may be due different mechanisms against classes of drugs. These are usually found the same organism, giving rise multidrug-resistant (MDR) extensively drug-resistant (XDR) bacteria. One mechanism that closely associated emergence MDR XDR bacteria efflux drugs since pump can transport In Gram-negative bacteria, pumps present two configurations: transmembrane protein anchored inner membrane complex formed by three proteins. The tripartite has membrane, periplasmic protein, porin outer membrane.

Language: Английский

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Translating eco-evolutionary biology into therapy to tackle antibiotic resistance

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(10), P. 671 - 685

Published: May 19, 2023

Language: Английский

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Biofilm Resilience: Molecular Mechanisms Driving Antibiotic Resistance in Clinical Contexts

Biology, Journal Year: 2025, Volume and Issue: 14(2), P. 165 - 165

Published: Feb. 6, 2025

Healthcare-associated infections pose a significant global health challenge, negatively impacting patient outcomes and burdening healthcare systems. A major contributing factor to healthcare-associated is the formation of biofilms, structured microbial communities encased in self-produced extracellular polymeric substance matrix. Biofilms are critical disease etiology antibiotic resistance, complicating treatment infection control efforts. Their inherent resistance mechanisms enable them withstand therapies, leading recurrent increased morbidity. This review explores development biofilms their dual roles disease. It highlights structural protective functions EPS matrix, which shields populations from immune responses antimicrobial agents. Key molecular biofilm including restricted penetration, persister cell dormancy, genetic adaptations, identified as barriers effective management. implicated various clinical contexts, chronic wounds, medical device-associated infections, oral complications, surgical site infections. prevalence hospital environments exacerbates challenges underscores urgent need for innovative preventive therapeutic strategies. evaluates cutting-edge approaches such DNase-mediated disruption, RNAIII-inhibiting peptides, DNABII proteins, bacteriophage nanoparticle-based solutions, coatings, lock therapies. also examines associated with biofilm-related diagnostic difficulties, disinfectant economic implications. emphasizes multidisciplinary approach importance understanding dynamics, role pathogenesis, advancements strategies combat biofilm-associated effectively settings. These insights aim enhance reduce burden diseases.

Language: Английский

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Dual-function regulator MexL as a target to control phenazines production and pathogenesis of Pseudomonas aeruginosa

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 26, 2025

Antibiotic resistance or tolerance of pathogens has become one the global public crises. Finding new drug targets may open up a way infection control. Phenazine pyocyanin (PYO) is an important virulence factor produced by pathogen Pseudomonas aeruginosa. Here we show that multidrug efflux pump repressor, MexL, acts as transcriptional activator to enhance phenazines production via binding with conserved DNA motif within promoters biosynthesis genes. Moreover, PYO functions self-regulating ligand MexL for restricting its own and mexL knockout attenuates antibiotics P. Based on structure resolve, find two antimicrobials can interact reduce Our in vivo studies suggest combination using MexL-antagonists bacterial efficacy common be effective combat aeruginosa infection. microbial infections. In this work, authors present molecular basis dual-function regulator target control pathogenesis opportunistic

Language: Английский

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Efflux in Gram-negative bacteria: what are the latest opportunities for drug discovery?

Expert Opinion on Drug Discovery, Journal Year: 2023, Volume and Issue: 18(6), P. 671 - 686

Published: May 18, 2023

Introduction The resistance-nodulation-division (RND) family is the most important group of multidrug efflux pumps in Gram-negative bacteria. Their inhibition increases susceptibility these microorganisms to antibiotics. study effect pumps' overexpression on bacterial physiology antibiotic-resistant mutants allows for identification exploitable weaknesses associated with resistance acquisition.Areas covered authors describe different RND strategies and provide examples inhibitors. This review also discusses inducers expression pumps, used human therapy that can produce transient antibiotics vivo. Since may have a role virulence, use systems as targets search antivirulence compounds discussed. Finally, this analyzes how trade-offs acquisition mediated by guide tackle such resistance.Expert opinion Increasing knowledge regulation, structure function provides information rational design pump These inhibitors would increase several and, occasionally, will reduce virulence. Furthermore, has serve develop new anti-resistance strategies.

Language: Английский

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Efflux pumps of Pseudomonas aeruginosa and their regulatory mechanisms underlying multidrug resistance

International Biodeterioration & Biodegradation, Journal Year: 2025, Volume and Issue: 202, P. 106096 - 106096

Published: April 14, 2025

Language: Английский

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Multidrug efflux pumps of Pseudomonas aeruginosa show selectivity for their natural substrates

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Antibiotic-resistant Gram-negative bacteria are an increasing threat to human health. Strategies restore antibiotic efficacy include targeting multidrug efflux pumps by competitive pump inhibitors. These could be derived from natural substrates of these systems. In this work, we aimed elucidate the clinically relevant Mex Pseudomonas aeruginosa untargeted metabolomic approach. We constructed a PA14 mutant, genetically deleted in major MexAB-OprM, MexCD-OprJ, MexXY-OprM, and MexEF-OprN expressed mutant each individually inducible promoter. Comparative analysis exo-metabolomes identified 210 features that were more abundant supernatant overexpressors compared pump-deficient mutant. Most specific, while only few shared among several pumps. by-products secondary metabolites as well signaling molecules. Supernatants also showed decreased accumulation fatty acids, including long chain homoserine lactone quorum sensing Our data suggests P. appear have dedicated roles extruding molecules, metabolic by-products, oxidized acids. findings represent interesting starting point for development

Language: Английский

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Fuzheng Touxie Jiedu Huayu Decoction inhibits the MexAB-OprM efflux pump and quorum sensing-mediated biofilm formation in difficult-to-treat multidrug resistance Pseudomonas aeruginosa

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 332, P. 118365 - 118365

Published: May 23, 2024

Fuzheng Touxie Jiedu Huayu Decoction (FTJHD) is a commonly used clinical formula that has been found effective in resisting multidrug resistance-Pseudomonas aeruginosa previous vivo and vitro studies.

Language: Английский

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Resistome Signature and Antibiotic Resistance Mechanisms in Rhizospheric Soil Bacteriomes of Mecca Region, Saudi Arabia: Insights into Impact on Human Health

Life, Journal Year: 2024, Volume and Issue: 14(8), P. 928 - 928

Published: July 24, 2024

The objective of this investigation is to ascertain the distinctive profile rhizospheric soil resistome within Mecca region, while also evaluating potential risks associated with horizontal transfer determinants open environment and human clinical isolates. We have made metagenomic whole-genome shotgun sequencing for microbiomes two endemic plants, namely Moringa oleifera Abutilon fruticosum. resistomes plants abundance antibiotic resistance genes (ARGs) were identified by cross-referencing encoded proteins comprehensive database (CARD). ARGs then analyzed their antimicrobial (AMR) mechanisms. Predominantly are bacterial species Pseudomonas aeruginosa Mycobacterium tuberculosis. These opportunistic pathogens implicated in respiratory infections correlated heightened mortality rates. most prevalent array existing comprises mexA, mexC, mexE, cpxR, mechanisms active efflux, along ACC(2), ACC(3), AAC(6), APH(6), addition arr1, arr3, arr4, iri, rphA, rphB, inactivation. Furthermore, vanS, vanR, vanJ target alteration, rpoB2 RbpA noted replacement protection, respectively. confer against a diverse spectrum drug classes encompassing fluoroquinolones, aminoglycosides, glycopeptides, rifampicins. This study underscores hazards posed health presence these pathogenic bacteria particularly scenarios where novel populations harbored subsequently transmitted through food chain Consequently, stringent adherence good agricultural transportation practices imperative, regard edible plant parts those utilized folkloric medicine.

Language: Английский

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Metagenome meta-analysis reveals an increase in the abundance of some multidrug efflux pumps and mobile genetic elements in chemically polluted environments

Applied and Environmental Microbiology, Journal Year: 2023, Volume and Issue: 89(10)

Published: Sept. 20, 2023

Many human activities contaminate terrestrial and aquatic environments with numerous chemical pollutants that not only directly alter the environment but also affect microbial communities in ways are potentially concerning to health, such as selecting for spread of antibiotic-resistance genes (ARGs) through horizontal gene transfer. In present study, metagenomes available public domain from polluted (with antibiotics, petroleum, metal mining, or coal-mining effluents) unpolluted were compared examine whether pollution has influenced abundance composition ARGs mobile elements, specific focus on IS26 class 1 integrons (intI1). When aggregated together, had a greater relative than intI1. general, pollution, notably was associated an increase prevalence linked multidrug efflux pumps. Included suite pumps mexK, mexB, mexF, mexW polyspecific whose substrate ranges include multiple classes critically important antibiotics. Also, some instances, β-lactam resistance (TEM181 OXA-541) increased, rifampicin (RNA polymerases subunits rpoB rpoB2) decreased abundance. This meta-analysis suggests different types can enrich populations carry pump systems medically critical antibiotics.IMPORTANCEThe United Nations identified being one three greatest threats environmental which evolution antimicrobial resistance, seminally health challenge, may be favored. While this is very plausible outcome continued there little evidence research evaluating risk. The objective study existing chemically evaluate increases genetic elements antibiotic resistance. key finding particularly exposed enriched, these confer antibiotics typically Pseudomonas spp. other Gram-negative bacteria. makes clear need more investigation impact reservoir their association contribute transfer events.

Language: Английский

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