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      N-alkylimidazole derivatives as potential inhibitors of quorum sensing in Pseudomonas aeruginosa

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          Abstract

          Antimicrobial resistance is a threat to global public health. Microbial resistance is mediated by biofilm formation and virulence behavior during infection. Quorum sensing (QS), a cell-to-cell communication is frequently used by microbes to evade host immune systems. Inhibiting QS channels is a potential route to halt microbial activities and eliminate them. Imidazole has been shown to be a potent warhead in various antimicrobial agents. This study aims to evaluate alkyl-imidazole derivatives as potential inhibitors of QS and to explore the interactions of the compounds with LasR, a key protein in the QS machinery of Pseudomonas aeruginosa. The study revealed that imidazole derivatives with longer alkyl chains possessed better antimicrobial activities. Octylimidazole and decylimidazole emerged as compounds with better anti-virulence and biofilm inhibition properties while hexylimidazole showed the best inhibitory activity against Pseudomonas aeruginosa PAO1. The binding affinity of the compounds with LasR followed a similar trend as that observed in the QS inhibitory assays, suggesting that interaction with LasR may be important for QS inhibition.

          Abstract

          Pyocyanin; LasR; Virulence factor; Biofilm inhibition; Imidazole derivatives.

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          The hierarchy quorum sensing network in Pseudomonas aeruginosa

          Jasmine Lee, Lianhui Zhang (2014)
          Pseudomonas aeruginosa causes severe and persistent infections in immune compromised individuals and cystic fibrosis sufferers. The infection is hard to eradicate as P. aeruginosa has developed strong resistance to most conventional antibiotics. The problem is further compounded by the ability of the pathogen to form biofilm matrix, which provides bacterial cells a protected environment withstanding various stresses including antibiotics. Quorum sensing (QS), a cell density-based intercellular communication system, which plays a key role in regulation of the bacterial virulence and biofilm formation, could be a promising target for developing new strategies against P. aeruginosa infection. The QS network of P. aeruginosa is organized in a multi-layered hierarchy consisting of at least four interconnected signaling mechanisms. Evidence is accumulating that the QS regulatory network not only responds to bacterial population changes but also could react to environmental stress cues. This plasticity should be taken into consideration during exploration and development of anti-QS therapeutics.
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            Outer membrane permeability and antibiotic resistance.

            Anne H. Delcour (2009)
            To date most antibiotics are targeted at intracellular processes, and must be able to penetrate the bacterial cell envelope. In particular, the outer membrane of gram-negative bacteria provides a formidable barrier that must be overcome. There are essentially two pathways that antibiotics can take through the outer membrane: a lipid-mediated pathway for hydrophobic antibiotics, and general diffusion porins for hydrophilic antibiotics. The lipid and protein compositions of the outer membrane have a strong impact on the sensitivity of bacteria to many types of antibiotics, and drug resistance involving modifications of these macromolecules is common. This review will describe the molecular mechanisms for permeation of antibiotics through the outer membrane, and the strategies that bacteria have deployed to resist antibiotics by modifications of these pathways.
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              Critical review on biofilm methods.

              Joana Azeredo, Nuno F Azevedo, Romain Briandet … (2017)
              Biofilms are widespread in nature and constitute an important strategy implemented by microorganisms to survive in sometimes harsh environmental conditions. They can be beneficial or have a negative impact particularly when formed in industrial settings or on medical devices. As such, research into the formation and elimination of biofilms is important for many disciplines. Several new methodologies have been recently developed for, or adapted to, biofilm studies that have contributed to deeper knowledge on biofilm physiology, structure and composition. In this review, traditional and cutting-edge methods to study biofilm biomass, viability, structure, composition and physiology are addressed. Moreover, as there is a lack of consensus among the diversity of techniques used to grow and study biofilms. This review intends to remedy this, by giving a critical perspective, highlighting the advantages and limitations of several methods. Accordingly, this review aims at helping scientists in finding the most appropriate and up-to-date methods to study their biofilms.
              Article 0 comments Cited 315 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Lawrence Sheringham Borquaye
                Journal
                Journal ID (nlm-ta): Heliyon
                Journal ID (iso-abbrev): Heliyon
                Title: Heliyon
                Publisher: Elsevier
                ISSN (Electronic): 2405-8440
                Publication date PMC-release: 25 December 2022
                Publication date Collection: December 2022
                Publication date (Electronic): 25 December 2022
                Volume: 8
                Issue: 12
                Electronic Location Identifier: e12581
                Affiliations
                [a ]Department of Chemistry, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                [b ]Central Laboratory, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                [c ]Department of Pharmacognosy, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                Author notes
                Article
                Publisher Item ID: S2405-8440(22)03869-5 Publisher ID: e12581
                DOI: 10.1016/j.heliyon.2022.e12581
                PMC ID: 9834748
                PubMed ID: 36643307
                SO-VID: 8f2b5662-62ce-4cb5-8894-a1e6a38cd177
                Copyright © © 2022 The Author(s)
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 26 July 2022
                Date revision received : 20 October 2022
                Date accepted : 15 December 2022
                Categories
                Subject: Research Article

                Keywords: pyocyanin,lasr,virulence factor,biofilm inhibition,imidazole derivatives
                Data availability:
                Keywords: pyocyanin, lasr, virulence factor, biofilm inhibition, imidazole derivatives

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