Common plant flavonoids prevent the assembly of amyloid curli fibres and can interfere with bacterial biofilm formation
TL;DR: Based on their strong and direct anti-amyloidogenic activities, distinct plant flavonoids may provide an attractive strategy to specifically combat amyloid-based biofilms of some relevant pathogens.
Abstract: Like all macroorganisms, plants have to control bacterial biofilm formation on their surfaces. On the other hand, biofilms are highly tolerant against antimicrobial agents and other stresses. Consequently, biofilms are also involved in human chronic infectious diseases, which generates a strong demand for anti-biofilm agents. Therefore, we systematically explored major plant flavonoids as putative anti-biofilm agents using different types of biofilms produced by Gram-negative and Gram-positive bacteria. In Escherichia coli macrocolony biofilms, the flavone luteolin and the flavonols myricetin, morin and quercetin were found to strongly reduce the extracellular matrix. These agents directly inhibit the assembly of amyloid curli fibres by driving CsgA subunits into an off-pathway leading to SDS-insoluble oligomers. In addition, they can interfere with cellulose production by still unknown mechanisms. Submerged biofilm formation, however, is hardly affected. Moreover, the same flavonoids tend to stimulate macrocolony and submerged biofilm formation by Pseudomonas aeruginosa. For Bacillus subtilis, the flavonone naringenin and the chalcone phloretin were found to inhibit growth. Thus, plant flavonoids are not general anti-biofilm compounds but show species-specific effects. However, based on their strong and direct anti-amyloidogenic activities, distinct plant flavonoids may provide an attractive strategy to specifically combat amyloid-based biofilms of some relevant pathogens.
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TL;DR: The iron-mobilizing activity of coumarins facilitates iron uptake from the soil environment, while their selective antimicrobial activity shapes the root microbiome, resulting in promotion of plant growth and health.
79 citations
TL;DR: The antimicrobial activity of quercetin is summarized with a special focus on its mechanistic principle, and the implications for its use as a clinically relevant antimicrobial agent are summarized.
Abstract: Quercetin, an essential plant flavonoid, possesses a variety of pharmacological activities. Extensive literature investigates its antimicrobial activity and possible mechanism of action. Quercetin has been shown to inhibit the growth of different Gram-positive and Gram-negative bacteria as well as fungi and viruses. The mechanism of its antimicrobial action includes cell membrane damage, change of membrane permeability, inhibition of synthesis of nucleic acids and proteins, reduction of expression of virulence factors, mitochondrial dysfunction, and preventing biofilm formation. Quercetin has also been shown to inhibit the growth of various drug-resistant microorganisms, thereby suggesting its use as a potent antimicrobial agent against drug-resistant strains. Furthermore, certain structural modifications of quercetin have sometimes been shown to enhance its antimicrobial activity compared to that of the parent molecule. In this review, we have summarized the antimicrobial activity of quercetin with a special focus on its mechanistic principle. Therefore, this review will provide further insights into the scientific understanding of quercetin’s mechanism of action, and the implications for its use as a clinically relevant antimicrobial agent.
59 citations
TL;DR: In this article, the authors focus on the contribution of molecular events to protein aggregation based on the analysis of kinetic profiles of aggregation and discuss the effect of inhibitors which target various species of aggregation pathways on the kinetic profile of protein aggregation.
28 citations
TL;DR: In this article, the authors present an overview of the most interesting results obtained in the research focused on the study of the interactions between flavonoids and bacterial proteins, which demonstrate the great potential of these compounds in developing innovative systems, which can help address the increasingly serious problem of antibiotic resistance.
Abstract: Flavonoids are among the most abundant natural bioactive compounds produced by plants. Many different activities have been reported for these secondary metabolites against numerous cells and systems. One of the most interesting is certainly the antimicrobial, which is stimulated through various molecular mechanisms. In fact, flavonoids are effective both in directly damaging the envelope of Gram-negative and Gram-positive bacteria but also by acting toward specific molecular targets essential for the survival of these microorganisms. The purpose of this paper is to present an overview of the most interesting results obtained in the research focused on the study of the interactions between flavonoids and bacterial proteins. Despite the great structural heterogeneity of these plant metabolites, it is interesting to observe that many flavonoids affect the same cellular pathways. Furthermore, it is evident that some of these compounds interact with more than one target, producing multiple effects. Taken together, the reported data demonstrate the great potential of flavonoids in developing innovative systems, which can help address the increasingly serious problem of antibiotic resistance.
25 citations
TL;DR: The properties of functional amyloids are a much-needed corrective to the unfortunate association of amyloid with neurodegenerative disease and a testimony to nature’s ability to get the best out of a protein fold.
Abstract: Functional amyloid is produced by many organisms but is particularly well understood in bacteria, where proteins such as CsgA (E. coli) and FapC (Pseudomonas) are assembled as functional bacterial amyloid (FuBA) on the cell surface in a carefully optimized process. Besides a host of helper proteins, FuBA formation is aided by multiple imperfect repeats which stabilize amyloid and streamline the aggregation mechanism to a fast-track assembly dominated by primary nucleation. These repeats, which are found in variable numbers in Pseudomonas, are most likely the structural core of the fibrils, though we still lack experimental data to determine whether the repeats give rise to β-helix structures via stacked β-hairpins (highly likely for CsgA) or more complicated arrangements (possibly the case for FapC). The response of FuBA fibrillation to denaturants suggests that nucleation and elongation involve equal amounts of folding, but protein chaperones preferentially target nucleation for effective inhibition. Smart peptides can be designed based on these imperfect repeats and modified with various flanking sequences to divert aggregation to less stable structures, leading to a reduction in biofilm formation. Small molecules such as EGCG can also divert FuBA to less organized structures, such as partially-folded oligomeric species, with the same detrimental effect on biofilm. Finally, the strong tendency of FuBA to self-assemble can lead to the formation of very regular two-dimensional amyloid films on structured surfaces such as graphite, which strongly implies future use in biosensors or other nanobiomaterials. In summary, the properties of functional amyloid are a much-needed corrective to the unfortunate association of amyloid with neurodegenerative disease and a testimony to nature’s ability to get the best out of a protein fold.
12 citations
References
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Book•
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26,898 citations
"Common plant flavonoids prevent the..." refers methods in this paper
...β-galactosidase activity was assayed by using onitrophenyl-β-D-galactopyranoside as a substrate and is reported as μmol of o-nitrophenol per min per mg of cellular protein (Miller, 1972)....
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TL;DR: Improvements in understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
Abstract: Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
11,162 citations
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TL;DR: The functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth are described.
Abstract: The microorganisms in biofilms live in a self-produced matrix of hydrated extracellular polymeric substances (EPS) that form their immediate environment. EPS are mainly polysaccharides, proteins, nucleic acids and lipids; they provide the mechanical stability of biofilms, mediate their adhesion to surfaces and form a cohesive, three-dimensional polymer network that interconnects and transiently immobilizes biofilm cells. In addition, the biofilm matrix acts as an external digestive system by keeping extracellular enzymes close to the cells, enabling them to metabolize dissolved, colloidal and solid biopolymers. Here we describe the functions, properties and constituents of the EPS matrix that make biofilms the most successful forms of life on earth.
7,041 citations
"Common plant flavonoids prevent the..." refers background in this paper
...By forming a cohesive polymer network, matrix components mediate bacterial surface adhesion, provide for mechanical stability of biofilms and protect bacteria against the detrimental effects of chemical insults and other environmental challenges (Flemming and Wingender, 2010)....
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...Matrix EPS include various exopolysaccharides, secreted proteins some of which can form amyloid fibres, extracellular DNA and lipids (Flemming and Wingender, 2010)....
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TL;DR: Several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.
3,630 citations
"Common plant flavonoids prevent the..." refers background in this paper
...They are known for their antioxidant, anti-inflammatory, antibacterial, antiviral, antiprotozoan, antifungal, anticancer and antiallergic properties that can promote human health and reduce the risk of diseases (Havsteen, 2002; Cushnie and Lamb, 2005, 2011; Gorniak and Bartoszewski, 2019)....
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...As a major class of secondary plant compounds, to which numerous beneficial effects also for human physiology have been ascribed (Havsteen, 2002; Cushnie and Lamb, 2005, 2011; Gorniak and Bartoszewski, 2019), we chose to test representatives of widespread plant flavonoids for anti-biofilm activity,…...
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TL;DR: The structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production are highlighted.
Abstract: There has been increasing interest in the research on flavonoids from plant sources because of their versatile health benefits reported in various epidemiological studies. Since flavonoids are directly associated with human dietary ingredients and health, there is need to evaluate structure and function relationship. The bioavailability, metabolism, and biological activity of flavonoids depend upon the configuration, total number of hydroxyl groups, and substitution of functional groups about their nuclear structure. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. Most recent researches have focused on the health aspects of flavonoids for humans. Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators. For pharmaceutical purposes cost-effective bulk production of different types of flavonoids has been made possible with the help of microbial biotechnology. This review highlights the structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production.
3,107 citations
"Common plant flavonoids prevent the..." refers background in this paper
...Interestingly, most flavonoids occur in glycosylated forms in plants (Cushnie and Lamb, 2011; Kumar and Pandey, 2013), but bacterial metabolism (also in our intestinal microbiota, see below) generates aglycones (Eid et al....
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...Interestingly, most flavonoids occur in glycosylated forms in plants (Cushnie and Lamb, 2011; Kumar and Pandey, 2013), but bacterial metabolism (also in our intestinal microbiota, see below) generates aglycones (Eid et al., 2014)....
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