Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa

Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system. is an archetypal biofilm-forming organism that utilizes a biofilm growth strat...

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Veröffentlicht in:Antimicrobial agents and chemotherapy 2017-05, Vol.61 (5)
Hauptverfasser: van Tilburg Bernardes, Erik, Charron-Mazenod, Laetitia, Reading, David J, Reckseidler-Zenteno, Shauna L, Lewenza, Shawn
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container_issue 5
container_start_page
container_title Antimicrobial agents and chemotherapy
container_volume 61
creator van Tilburg Bernardes, Erik
Charron-Mazenod, Laetitia
Reading, David J
Reckseidler-Zenteno, Shauna L
Lewenza, Shawn
description Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system. is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in cystic fibrosis (CF) patients. The extracellular matrix of biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and nonmucoid isolates of produce the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation, and immune evasion. Given the central importance of the EPS for biofilms, they are attractive targets for novel anti-infective compounds. In this study, we used a high-throughput gene expression screen to identify compounds that repress expression of the genes. The repressors demonstrated antibiofilm activity against microplate and flow chamber biofilms formed by wild-type and hyperbiofilm-forming strains. To determine the potential role of EPS in virulence, / mutants were shown to have reduced virulence in feeding behavior and slow killing virulence assays in The antibiofilm molecules also reduced PAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds increased killing of biofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronic infections.
doi_str_mv 10.1128/AAC.01997-16
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subjects Animals
Anti-Bacterial Agents
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Biofilms
Biofilms - growth & development
Caenorhabditis elegans
Caenorhabditis elegans - microbiology
Clinical Therapeutics
DNA, Bacterial - metabolism
Extracellular Matrix - drug effects
Extracellular Matrix - microbiology
High-Throughput Screening Assays
Humans
Nematoda
Polysaccharides, Bacterial
Polysaccharides, Bacterial - antagonists & inhibitors
Polysaccharides, Bacterial - metabolism
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Pseudomonas aeruginosa - isolation & purification
Pseudomonas aeruginosa - pathogenicity
Pseudomonas Infections - drug therapy
Pseudomonas Infections - microbiology
Repressor Proteins
Repressor Proteins - metabolism
Repressor Proteins - pharmacology
Virulence - genetics
title Exopolysaccharide-Repressing Small Molecules with Antibiofilm and Antivirulence Activity against Pseudomonas aeruginosa
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