The Molecular Architecture of Pseudomonas aeruginosa Quorum-Sensing Inhibitors

Li, Qiaoqiang; Shen, Mo; Wang, Hong; Ye, Xinyi

doi:10.3390/md20080488

Cited by 24 publications

(10 citation statements)

References 170 publications

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“…Pseudomonas aeruginosa is known to be responsible for hospital-acquired infections, particularly in immunocompromized patients and patients with cystic fibrosis (Eberl and Tümmler 2004 , Palleroni 2010 ). The QS of P. aeruginosa PA14 involves two major AHL-based QS systems, the LasIR and RhlIR, which produce C 4 -HSL and 3-oxo-C 12 -HSL (Li et al 2022 ). In this experimental set-up, no AHL was detected by the reporter strain C. violaceum CV026 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Disrupting quorum sensing as a strategy to inhibit bacterial virulence in human, animal, and plant pathogens

Gonzales,

Kergaravat,

Jacquet

et al. 2024

Pathogens and Disease

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The development of sustainable alternatives to conventional antimicrobials is needed to address bacterial virulence while avoiding selecting resistant strains in a variety of fields, including human, animal and plant health. Quorum sensing (QS), a bacterial communication system involved in noxious bacterial phenotypes such as virulence, motility and biofilm formation, is of utmost interest. In this study, we harnessed the potential of the lactonase SsoPox to disrupt QS of human, fish, and plant pathogens. Lactonase treatment significantly alters phenotypes including biofilm formation, motility, and infection capacity. In plant pathogens, SsoPox decreased the production of plant cell wall degrading enzymes in Pectobacterium atrosepticum and reduced the maceration of onions infected by Burkholderia glumae. In human pathogens, lactonase treatment significantly reduced biofilm production in Acinetobacter baumannii, Burkholderia cepacia and Pseudomonas aeruginosa, with the cytotoxicity of the latter being reduced by SsoPox treatment. In fish pathogens, lactonase treatment inhibited biofilm formation and bioluminescence in Vibrio harveyi and affected QS regulation in Aeromonas salmonicida. QS inhibition can thus be used to largely impact the virulence of bacterial pathogens and would constitute a global and sustainable approach for public, crop and livestock health in line with the expectations of the One Health initiative.

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Section: Resultsmentioning

confidence: 99%

Disrupting quorum sensing as a strategy to inhibit bacterial virulence in human, animal, and plant pathogens

Gonzales,

Kergaravat,

Jacquet

et al. 2024

Pathogens and Disease

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show abstract

“…Similarly, it was found the binding of lasR with V-06-018, (a small QSI) directly interferes with the native ligand-binding sites in lasR and stabilizes this inactive interaction, thereby preventing dimerization and binding with DNA [ 57 ]. To inhibit the binding between odDHL and lasR of P. aeruginosa , several novel QSI compounds were created by replacing the lactone ring of odDHL with the pyrone ring or altering the length of the alkyl chain [ 58 ]. The docking results provided evidence that H-bonding and hydrophobic interactions with amino acid residues are crucial for understanding the molecular mechanisms involved in the QSI activity of pyridoxal lactohydrazone [ 59 ].…”

Section: Discussionmentioning

confidence: 99%

Quenching of quorum sensing in multi-drug resistant Pseudomonas aeruginosa: insights on halo-bacterial metabolites and gamma irradiation as channels inhibitors

Talaat,

Abu El-naga,

El-Bialy

et al. 2024

Ann Clin Microbiol Antimicrob

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Background Anti-virulence therapy is a promising strategy to treat multi-drug resistant (MDR) pathogens. Pseudomonas aeruginosa is a potent opportunistic pathogen because of an array of virulence factors that are regulated by quorum sensing systems. Methods The virulence features of four multi-drug resistant P. aeruginosa strains were investigated upon exposure to the sub-lethal dose of gamma rays (1 kGy), and sub-inhibitory concentrations of bioactive metabolites recovered from local halophilic strains in comparison to control. Then, the gene expression of AHL-mediated quorum sensing systems (las/rhl) was quantitatively determined in treated and untreated groups by real-time PCR. Results The bioactive metabolites recovered from halophilic strains previously isolated from saline ecosystems were identified as Halomonas cupida (Halo-Rt1), H. elongate (Halo-Rt2), Vigibacillus natechei (Halo-Rt3), Sediminibacillus terrae (Halo-Rt4) and H. almeriensis (Halo-Rt5). Results revealed that both gamma irradiation and bioactive metabolites significantly reduced the virulence factors of the tested MDR strains. The bioactive metabolites showed a maximum efficiency for inhibiting biofilm formation and rhamnolipids production whereas the gamma irradiation succeeded in decreasing other virulence factors to lower levels in comparison to control. Quantitative-PCR results showed that AHL-mediated quorum sensing systems (las/rhl) in P. aeruginosa strains were downregulated either by halo-bacterial metabolites or gamma irradiation in all treatments except the upregulation of both lasI internal gene and rhlR intact gene in P. aeruginosa NCR-RT3 and both rhlI internal gene and rhlR intact gene in P. aeruginosa U3 by nearly two folds or more upon exposure to gamma irradiation. The most potent result was observed in the expression of lasI internal gene that was downregulated by more than ninety folds in P. aeruginosa NCR-RT2 after treatment with metabolites of S. terrae (Halo-Rt4). Analyzing metabolites recovered from H. cupida (Halo-Rt1) and H. elongate (Halo-Rt2) using LC–ESI–MS/MS revealed many chemical compounds that have quorum quenching properties including glabrol, 5,8-dimethoxyquinoline-2-carbaldehyde, linoleoyl ethanolamide, agelasine, penigequinolones derivatives, berberine, tetracosanoic acid, and liquidambaric lactone in the former halophile and phloretin, lycoctonine, fucoxanthin, and crassicauline A in the latter one. Conclusion QS inhibitors can significantly reduce the pathogenicity of MDR P. aeruginosa strains; and thus can be an effective and successful strategy for treating antibiotic resistant traits.

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“…Among the QS mentioned above, the las system is at the top of the QS hierarchy and is required for optimal activation of the rhl and pqs systems QS. The las system includes two proteins, LasI (synthase) and LasR, while the rhl system includes the proteins RhlI (synthase) and RhlR [ 59 ]. Another example is the phytopathogenic soil bacterium Agrobacterium tumefaciens, which uses the determinants of the QS system belonging to the LuxR/LuxI class.…”

Section: Mechanism Of the Synthesis And Action Of Autoinducersmentioning

confidence: 99%

The Role of Quorum Sensing Molecules in Bacterial–Plant Interactions

et al. 2023

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Quorum sensing (QS) is a system of communication of bacterial cells by means of chemical signals called autoinducers, which modulate the behavior of entire populations of Gram-negative and Gram-positive bacteria. Three classes of signaling molecules have been recognized, Al-1, Al-2, Al-3, whose functions are slightly different. However, the phenomenon of quorum sensing is not only concerned with the interactions between bacteria, but the whole spectrum of interspecies interactions. A growing number of research results confirm the important role of QS molecules in the growth stimulation and defense responses in plants. Although many of the details concerning the signaling metabolites of the rhizosphere microflora and plant host are still unknown, Al-1 compounds should be considered as important components of bacterial–plant interactions, leading to the stimulation of plant growth and the biological control of phytopathogens. The use of class 1 autoinducers in plants to induce beneficial activity may be a practical solution to improve plant productivity under field conditions. In addition, researchers are also interested in tools that offer the possibility of regulating the activity of autoinducers by means of degrading enzymes or specific inhibitors (QSI). Current knowledge of QS and QSI provides an excellent foundation for the application of research to biopreparations in agriculture, containing a consortia of AHL-producing bacteria and QS inhibitors and limiting the growth of phytopathogenic organisms.

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The Molecular Architecture of Pseudomonas aeruginosa Quorum-Sensing Inhibitors

Cited by 24 publications

References 170 publications

Disrupting quorum sensing as a strategy to inhibit bacterial virulence in human, animal, and plant pathogens

Disrupting quorum sensing as a strategy to inhibit bacterial virulence in human, animal, and plant pathogens

Quenching of quorum sensing in multi-drug resistant Pseudomonas aeruginosa: insights on halo-bacterial metabolites and gamma irradiation as channels inhibitors

The Role of Quorum Sensing Molecules in Bacterial–Plant Interactions

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