Autoinducer Analogs Can Provide Bactericidal Activity to Macrolides in Pseudomonas aeruginosa through Antibiotic Tolerance Reduction

Macrolide antibiotics are used in treating Pseudomonas aeruginosa chronic biofilm infections despite their unsatisfactory antibacterial activity, because they display several special activities, such as modulation of the bacterial quorum sensing and immunomodulatory effects on the host. In this study, we investigated the effects of the newly synthesized P. aeruginosa quorum-sensing autoinducer analogs (AIA-1, -2) on the activity of azithromycin and clarithromycin against P. aeruginosa. In the killing assay of planktonic cells, AIA-1 and -2 enhanced the bactericidal ability of macrolides against P. aeruginosa PAO1; however, they did not affect the minimum inhibitory concentrations of macrolides. In addition, AIA-1 and -2 considerably improved the killing activity of azithromycin and clarithromycin in biofilm cells. The results indicated that AIA-1 and -2 could affect antibiotic tolerance. Moreover, the results of hydrocarbon adherence and cell membrane permeability assays suggested that AIA-1 and -2 changed bacterial cell surface hydrophobicity and accelerated the outer membrane permeability of the hydrophobic antibiotics such as azithromycin and clarithromycin. Our study demonstrated that the new combination therapy of macrolides and AIA-1 and -2 may improve the therapeutic efficacy of macrolides in the treatment of chronic P. aeruginosa biofilm infections.

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Grapefruit essential oils inhibit quorum sensing of Pseudomonas aeruginosa

Food Science and Technology International ◽

10.1177/1082013219883465 ◽

2019 ◽

Vol 26 (3) ◽

pp. 231-241 ◽

Cited By ~ 2

Author(s):

María C Luciardi ◽

M Amparo Blázquez ◽

María R Alberto ◽

Elena Cartagena ◽

Mario E Arena

Keyword(s):

Pseudomonas Aeruginosa ◽

Chemical Composition ◽

Quorum Sensing ◽

Essential Oils ◽

Citrus Paradisi ◽

Food Preservative ◽

Bacterial Quorum Sensing ◽

Citrus Essential Oils ◽

Bacterial Quorum ◽

Cold Pressed

Citrus essential oils are used in food to confer flavor and aromas. The citrus essential oils have been granted as GRAS and could be used as antimicrobial additives to control bacterial quorum sensing from potential food bacterial pathogens. The chemical composition and inhibitory activity of Citrus paradisi (grapefruit) essential oils obtained by cold-pressed method (EOP) and cold-pressed method followed by steam distillation, against Pseudomonas aeruginosa were determined . The GC-MS analyses of the oil indicated the amount of the essential oil components was highest with D-limonene in both cases. However, the extraction method modified the chemical composition. EOP had higher amount of coumarins and flavonoid as well as less oxygenated terpenoids. At 0.1 mg/mL essential oils were not able to modify the bacterial development but inhibited the P. aeruginosa biofilm production between 52% and 55%, sessile viability between 45% and 48%, autoinducer production and elastase activity between 30% and 56%. Limonene was less effective at inhibiting P. aeruginosa than the essential oils, suggesting a synergistic effect of the minor components. According to our results, grapefruit essential oils could be used as a food preservative to control P. aeruginosa virulence.

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Alkyne-Substituted Fimbrolide Analogues as Novel Bacterial Quorum-Sensing Inhibitors

Australian Journal of Chemistry ◽

10.1071/ch18194 ◽

2018 ◽

Vol 71 (9) ◽

pp. 708 ◽

Cited By ~ 2

Author(s):

Nripendra Nath Biswas ◽

George M. Iskander ◽

Marcin Mielczarek ◽

Tsz Tin Yu ◽

David StC Black ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Cell Communication ◽

Social Adaptation ◽

Sonogashira Reaction ◽

Coupling Reactions ◽

Bacterial Quorum Sensing ◽

Bacterial Quorum ◽

High Yields ◽

Brominated Furanones

Gram-negative bacteria such as Pseudomonas aeruginosa use furanosyl diesters as autoinducers for quorum sensing (QS), a major regulatory and cell-to-cell communication system for social adaptation, virulence factor production, biofilm formation, and antibiotic resistance. A range of natural and synthetic brominated furanones, i.e. fimbrolide derivatives, have been found to act as inhibitors of QS-dependent bacterial phenotypes, complementing the bactericidal ability of traditional antibiotics. In this work, several novel acetylene analogues of fimbrolides were synthesised in moderate to high yields via Sonogashira coupling reactions of brominated furanones 4-bromo-5-(bromomethylene)furan-2(5H)-one 4 and 5-(dibromomethylene)-3-ethylfuran-2(5H)-one 5. The Sonogashira reaction of acetylenes on 4-bromo-5-(bromomethylene)furan-2(5H)-one 4 was favoured at the C5 methylene bromide over the C4 bromide substituent. On biological testing, the most potent compounds 13 and 14 showed 82 and 98 % bacterial quorum-sensing inhibitory (QSI) activity against Pseudomonas aeruginosa reporter strain respectively.

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Corrigendum to “Serotonin Activates Bacterial Quorum Sensing and Enhances the Virulence of Pseudomonas aeruginosa in the Host” [EBioMedicine 9 (2016) 161–169]

EBioMedicine ◽

10.1016/j.ebiom.2017.07.025 ◽

2017 ◽

Vol 23 ◽

pp. 195

Author(s):

Leslie D. Knecht ◽

Gregory O'Connor ◽

Rahul Mittal ◽

Xue Z. Liu ◽

Pirouz Daftarian ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Bacterial Quorum Sensing ◽

Bacterial Quorum

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Serotonin Activates Bacterial Quorum Sensing and Enhances the Virulence of Pseudomonas aeruginosa in the Host

EBioMedicine ◽

10.1016/j.ebiom.2016.05.037 ◽

2016 ◽

Vol 9 ◽

pp. 161-169 ◽

Cited By ~ 30

Author(s):

Leslie D. Knecht ◽

Gregory O'Connor ◽

Rahul Mittal ◽

Xue Z. Liu ◽

Pirouz Daftarian ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Bacterial Quorum Sensing ◽

Bacterial Quorum

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Novel detection of specific bacterial quorum sensing molecules in saliva: Potential non-invasive biomarkers for pulmonary Pseudomonas aeruginosa in cystic fibrosis

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2021.08.030 ◽

2021 ◽

Author(s):

Karmel Webb ◽

Miguel Cámara ◽

Nur Masirah M. Zain ◽

Nigel Halliday ◽

Kenneth D. Bruce ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Non Invasive ◽

Bacterial Quorum Sensing ◽

Bacterial Quorum

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Histological assessment, anti-quorum sensing, and anti-biofilm activities of Dioon spinulosum extract: in vitro and in vivo approach

Scientific Reports ◽

10.1038/s41598-021-03953-x ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Engy Elekhnawy ◽

Walaa A. Negm ◽

Mona El-Aasr ◽

Amal Abo Kamer ◽

Mohammed Alqarni ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Biofilm Formation ◽

Cell Surface Hydrophobicity ◽

Fibroblast Cell ◽

Surface Hydrophobicity ◽

Human Skin Fibroblast ◽

Electron Microscopes

AbstractPseudomonas aeruginosa is an opportunistic bacterium causing several health problems and having many virulence factors like biofilm formation on different surfaces. There is a significant need to develop new antimicrobials due to the spreading resistance to the commonly used antibiotics, partly attributed to biofilm formation. Consequently, this study aimed to investigate the anti-biofilm and anti-quorum sensing activities of Dioon spinulosum, Dyer Ex Eichler extract (DSE), against Pseudomonas aeruginosa clinical isolates. DSE exhibited a reduction in the biofilm formation by P. aeruginosa isolates both in vitro and in vivo rat models. It also resulted in a decrease in cell surface hydrophobicity and exopolysaccharide quantity of P. aeruginosa isolates. Both bright field and scanning electron microscopes provided evidence for the inhibiting ability of DSE on biofilm formation. Moreover, it reduced violacein production by Chromobacterium violaceum (ATCC 12,472). It decreased the relative expression of 4 quorum sensing genes (lasI, lasR, rhlI, rhlR) and the biofilm gene (ndvB) using qRT-PCR. Furthermore, DSE presented a cytotoxic activity with IC50 of 4.36 ± 0.52 µg/ml against human skin fibroblast cell lines. For the first time, this study reports that DSE is a promising resource of anti-biofilm and anti-quorum sensing agents.

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Characterization of LasR protein involved in bacterial quorum sensing mechanism of Pseudomonas aeruginosa

Biotechnology and Bioprocess Engineering ◽

10.1007/s12257-008-0188-z ◽

2009 ◽

Vol 14 (2) ◽

pp. 146-154 ◽

Cited By ~ 10

Author(s):

Hai Bo Liu ◽

Kyong Pyo Koh ◽

Joon Hee Lee ◽

Jung Sun Kim ◽

Sunghoon Park

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Sensing Mechanism ◽

Bacterial Quorum Sensing ◽

Bacterial Quorum

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Polyphenols from Salix tetrasperma Impair Virulence and Inhibit Quorum Sensing of Pseudomonas aeruginosa

Molecules ◽

10.3390/molecules25061341 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1341 ◽

Cited By ~ 4

Author(s):

Islam Mostafa ◽

Hisham A. Abbas ◽

Mohamed L. Ashour ◽

Abdelaziz Yasri ◽

Assem M. El-Shazly ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Secondary Metabolites ◽

Bacterial Resistance ◽

Stem Bark ◽

Dependent Manner ◽

Active Components ◽

Quorum Sensing Inhibitors ◽

Bacterial Quorum Sensing ◽

Bacterial Quorum

Bacterial resistance represents one of the emerging obstacles in plants, animals, and humans that impairs treatment with antibacterial agents. Targeting of the bacterial quorum sensing system is one of the strategies to overcome this problem. Recently, research has been focused on natural and food components which can function as quorum sensing inhibitors. In this study, a methanol extract from Salix tetrasperma stem bark was phytochemically profiled by LC-MS analysis. This resulted in the identification of 38 secondary metabolites with (epi)catechin-(epi)catechin, epicatechin, tremulacin, salicortin, and trichocarposide as the major constituents. The extracts of both stem bark and the previously profiled flower of S. tetrasperma were tested for anti-quorum sensing activity in a common and widely distributed pathogen Pseudomonas aeruginosa. The natural products inhibited swimming and swarming motilities, as well as proteolytic and hemolytic activities in a dose-dependent manner. Molecular docking of the constituents from both extracts against the quorum sensing controlling systems Lasl/LasR, rhll/rhlR, and PQS/MvfR showed that epicatechin, (epi)catechin-(epi)catechin, p-hydroxy benzoyl galloyl glucose, p-hydroxy benzoyl protocatechuic acid glucose, and caffeoylmalic acid could be the main active components. This study supports the importance of secondary metabolites, especially polyphenols, as quorum sensing inhibitors.

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Sulforaphane and erucin, natural isothiocyanates from broccoli, inhibit bacterial quorum sensing

MedChemComm ◽

10.1039/c2md20196h ◽

2013 ◽

Vol 4 (1) ◽

pp. 175-179 ◽

Cited By ~ 49

Author(s):

Hadas Ganin ◽

Josep Rayo ◽

Neri Amara ◽

Niva Levy ◽

Pnina Krief ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Cruciferous Vegetables ◽

Bacterial Quorum Sensing ◽

Bacterial Quorum

Sulforaphane and erucin, two natural isothiocyanates that are highly abundant in broccoli and other cruciferous vegetables, were found to strongly inhibit quorum sensing and virulence in Pseudomonas aeruginosa.

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