S. Jaya Prabhavathi1 , K. Subrahmaniyan2 , M. Senthil Kumar3 , G. Gayathry4 , G. Malathi5*
1Regional Research Station, Tamil Nadu Agricultural University, Vridhachalam, 606 001 Cuddalore District, Tamil Nadu, India
2Tamil Nadu Rice Research Institute, Aduthurai - 612 101-India
3Horticultural Research Station, Yercaud-Tamil Nadu, India
4ICAR- TNAU, Krishi Vigyan Kendra, Vridhachalam – 606 001, Cuddalore District, Tamil Nadu,
5ICAR Krishi Vigyan Kendra, Sandhiyur, Salem PIN - 636 203, India
Corresponding Author Email: malathihort@gmail.com
DOI : https://doi.org/10.51470/AGRI.2023.2.3.10
Abstract
Honey, a natural product derived from floral nectar and processed by bees, has long been recognized for its therapeutic properties. In recent years, extensive research has focused on exploring the antibacterial, anti-biofilm, and anti-quorum sensing activities of honey. This comprehensive review aims to summarize and analyze the current state of knowledge regarding the diverse antimicrobial properties of honey, with a particular emphasis on its effectiveness against bacterial infections, biofilm formation, and quorum sensing mechanisms. The review discusses the chemical composition of honey, including its various bioactive components, and examines their contributions to its antimicrobial effects. Furthermore, the mechanisms underlying honey’s antibacterial action, its ability to disrupt biofilm formation, and its interference with quorum sensing signaling pathways are elucidated. The review also highlights the potential applications of honey in clinical settings, wound management, and the development of novel therapeutic agents. By providing a thorough examination of the antibacterial, anti-biofilm, and anti-quorum sensing properties of honey, this review aims to contribute to a deeper understanding of its therapeutic potential and to inspire further research in this promising area.
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Introduction
Honey has been valued for centuries as a natural remedy for various ailments due to its remarkable antimicrobial properties. Ancient civilizations recognized honey’s ability to promote wound healing, prevent infections, and alleviate symptoms of illness [1]. In recent years, scientific research has provided insights into the multifaceted antimicrobial effects of honey, revealing its potential as a therapeutic agent against bacterial infections, biofilm-related diseases, and quorum sensing-mediated virulence in pathogens. This comprehensive review aims to explore the antibacterial, anti-biofilm, and anti-quorum sensing properties of honey, shedding light on its mechanisms of action and therapeutic applications in modern medicine. Honey, a natural product derived from the nectar of flowers and processed by honeybees, has been revered for centuries for its medicinal properties and culinary delights [2]. Beyond its sweet taste and culinary uses, honey has garnered increasing attention in recent years for its remarkable antimicrobial properties, particularly its ability to combat bacterial infections, disrupt biofilm formation, and interfere with quorum-sensing mechanisms in pathogens. This comprehensive review aims to delve into the multifaceted antimicrobial capabilities of honey, specifically focusing on its antibacterial, anti-biofilm, and anti-quorum sensing properties.
Historically, honey has been used in various cultures as a traditional remedy for a wide range of ailments, including wound healing, gastrointestinal disorders, and respiratory infections. Ancient civilizations recognized honey’s inherent antimicrobial properties, attributing its therapeutic effects to its acidic pH, low moisture content, and the production of hydrogen peroxide by the enzyme glucose oxidase [3]. However, recent scientific investigations have unveiled a wealth of additional bioactive components within honey that contribute to its potent antimicrobial activity.
The chemical composition of honey is highly complex and varies depending on factors such as floral sources, geographical origin, and processing methods. Honey comprises a diverse array of sugars, enzymes, organic acids, proteins, amino acids, vitamins, minerals, and phenolic compounds, each with its unique contribution to its antimicrobial effects [4]. Notably, hydrogen peroxide and methylglyoxal have emerged as key bioactive components in honey, exerting powerful bactericidal effects against a broad spectrum of bacterial pathogens. In addition to its direct antimicrobial effects, honey possesses the remarkable ability to inhibit biofilm formation and disrupt pre-formed biofilms, which are implicated in chronic infections and antibiotic resistance. Biofilms, complex microbial communities encased in a self-produced matrix of extracellular polymeric substances, pose significant challenges in clinical settings due to their enhanced resistance to antimicrobial agents and immune defences [5]. Honey’s ability to penetrate biofilm matrices, disrupt bacterial cell-cell communication, and interfere with quorum sensing signaling pathways makes it a promising therapeutic agent for combating biofilm-related infections. Furthermore, honey has been shown to interfere with quorum sensing mechanisms in bacterial pathogens, attenuating the expression of virulence genes, and reducing microbial pathogenicity [6]. Quorum sensing is a cell-to-cell communication system used by bacteria to coordinate gene expression in response to population density, regulating virulence factors, biofilm formation, and microbial pathogenesis. By disrupting quorum sensing signaling pathways, honey reduces bacterial virulence, impedes biofilm development, and enhances susceptibility to conventional antibiotics [7].
Figure 1. The main constituents attributed to honey’s antimicrobial activity and their mechanism of action. Direct inhibitory factors affect cellular mechanisms (blue), indirect inhibitory factors have a wide-ranging effect on the bacterial cell (green), copyright permission from MDPI and adopted from [21]. Honey exhibits potent antimicrobial activity attributed to its diverse array of constituents, each contributing to its effectiveness against bacteria. This figure outlines the main constituents responsible for honey’s antimicrobial properties along with their mechanisms of action.
Direct Inhibitory Factors (Blue):
1. Hydrogen Peroxide: Generated by the enzyme glucose oxidase, hydrogen peroxide acts as a potent antimicrobial agent by damaging bacterial cell membranes and DNA, leading to cell death.
2. Phenolic Compounds: Phenolic compounds such as flavonoids and phenolic acids exert direct antimicrobial effects by disrupting bacterial cell membranes, inhibiting enzymatic activity, and interfering with essential cellular processes.
3. Acidity: Honey’s acidic pH inhibits bacterial growth by disrupting cellular functions and metabolic processes, particularly in bacteria sensitive to acidic environments.
Indirect Inhibitory Factors (Green):
1. Osmotic Pressure: The high sugar concentration in honey creates a hyperosmotic environment that dehydrates bacterial cells, inhibiting their growth and metabolism.
2. Low Water Activity: Honey’s low water activity limits microbial growth by reducing the availability of free water essential for bacterial metabolism and proliferation.
3. Antibiotic Potentiation: Honey enhances the efficacy of conventional antibiotics by modulating bacterial resistance mechanisms, increasing antibiotic uptake, and synergistically enhancing antimicrobial activity.
4. Biofilm Disruption: Honey disrupts bacterial biofilms by interfering with quorum sensing mechanisms, inhibiting biofilm formation, and destabilizing pre-existing biofilm structures. By combining direct inhibitory factors that target specific cellular mechanisms with indirect inhibitory factors that exert a wider-ranging effect on bacterial cells, honey effectively inhibits bacterial growth, mitigates antibiotic resistance, and disrupts biofilm formation, making it a valuable natural antimicrobial agent.
In light of the increasing prevalence of antibiotic-resistant infections and the diminishing effectiveness of conventional antimicrobial agents, there is a growing interest in exploring alternative therapeutic strategies, such as natural products like honey. Understanding the mechanisms underlying honey’s antimicrobial properties and elucidating its therapeutic potential are crucial steps toward harnessing its benefits for clinical applications, wound management, and the development of novel antimicrobial agents [8]. This comprehensive review aims to provide a thorough examination of the antibacterial, anti-biofilm, and anti-quorum sensing properties of honey, drawing insights from the latest scientific literature and research findings. By synthesizing existing knowledge and identifying key areas for future research, this review seeks to advance our understanding of honey’s role in combating microbial infections and to inspire further exploration of its therapeutic applications in modern medicine.
Chemical Composition of Honey
Honey is a complex mixture of sugars, enzymes, organic acids, proteins, amino acids, vitamins, minerals, and phenolic compounds. Its composition varies depending on floral sources, geographical location, and processing methods. The bioactive components of honey, including hydrogen peroxide, methylglyoxal, phenolic acids, flavonoids, and peptides, contribute to its antimicrobial properties and therapeutic efficacy. Hydrogen peroxide, produced by the enzymatic activity of glucose oxidase, exhibits broad-spectrum antimicrobial activity against bacteria, fungi, and viruses. Methylglyoxal, a key component of manuka honey, possesses potent antibacterial properties attributed to its ability to damage bacterial proteins and DNA. The chemical composition of honey is highly complex and varies depending on several factors, including the floral sources from which bees collect nectar, environmental conditions, and bee species [9]. While honey is primarily composed of sugars, it also contains a diverse array of other compounds that contribute to its unique flavor, color, aroma, and therapeutic properties.
1. Sugars: The predominant sugars in honey are fructose and glucose, which together account for the majority of its carbohydrate content. These sugars are responsible for honey’s sweet taste and provide a source of energy.
2. Enzymes: Honey contains various enzymes that are derived from the salivary glands of bees and from plant nectar. The most notable enzyme in honey is glucose oxidase, which converts glucose into gluconic acid and hydrogen peroxide, contributing to honey’s antimicrobial properties.
3. Organic Acids: Organic acids such as gluconic acid, acetic acid, citric acid, and formic acid are present in honey in small quantities. These organic acids contribute to honey’s acidity and help inhibit the growth of microorganisms.
4. Proteins and Amino Acids: Honey contains trace amounts of proteins and amino acids, including enzymes, peptides, and free amino acids. These compounds play a role in honey’s nutritional value and contribute to its antioxidant properties.
5. Vitamins and Minerals: Honey contains small amounts of vitamins and minerals, including vitamin C, vitamin B complex, calcium, magnesium, potassium, and phosphorus. While the levels of vitamins and minerals in honey are relatively low, they contribute to its overall nutritional profile.
6. Phenolic Compounds: Phenolic compounds are a diverse group of secondary metabolites found in honey, including flavonoids, phenolic acids, and polyphenols. These compounds have antioxidant, anti-inflammatory, and antimicrobial properties, and contribute to the color and flavor of honey.
7. Other Bioactive Compounds: Honey also contains other bioactive compounds, such as antioxidants, flavonoids, and volatile organic compounds, which contribute to its therapeutic properties and sensory characteristics.
The chemical composition of honey can vary significantly depending on factors such as floral source, geographical location, climate, and processing methods. Different types of honey, such as clover honey, acacia honey, and manuka honey, may have distinct chemical profiles and therapeutic properties. Overall, the diverse array of compounds found in honey contributes to its multifaceted health benefits and therapeutic properties, including its antimicrobial, antioxidant, anti-inflammatory, and wound-healing effects [10]. Understanding the chemical composition of honey is essential for elucidating its mechanisms of action and exploring its potential applications in various fields, including medicine, nutrition, and food science.
Antibacterial Activity of Honey:
Honey exerts potent antibacterial effects against a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative species. Its antimicrobial action is mediated by multiple mechanisms, including osmotic effects, low pH, production of hydrogen peroxide, and the presence of non-peroxide bioactive compounds. The high sugar concentration in honey creates a hyperosmotic environment that dehydrates bacterial cells, inhibiting their growth and metabolism. Additionally, the acidic pH of honey disrupts bacterial cell membranes and enzymatic functions, further impeding microbial proliferation. Furthermore, the enzymatic generation of hydrogen peroxide in honey contributes to its oxidative stress-inducing effects on bacteria, leading to cell damage and death [11]. The antibacterial activity of honey is one of its most well-known and extensively studied properties. Honey has been used for centuries as a natural remedy for various bacterial infections, and modern scientific research has provided insights into the mechanisms underlying its antibacterial effects.
1. Hydrogen Peroxide Production: One of the primary mechanisms through which honey exerts its antibacterial activity is through the production of hydrogen peroxide. Honey contains the enzyme glucose oxidase, which catalyzes the conversion of glucose to gluconic acid and hydrogen peroxide. Hydrogen peroxide is a potent antimicrobial agent that can inhibit the growth of bacteria by damaging their cell membranes and DNA [12].
2. Low Water Activity: Honey has a low water activity, meaning that it contains very little free water available for microbial growth. The high sugar concentration in honey creates a hyperosmotic environment that dehydrates bacterial cells, inhibiting their growth and reproduction. Bacteria rely on water for various metabolic processes, and the low water activity of honey deprives them of this essential resource.
3. Acidic pH: The acidic pH of honey, typically ranging between 3.2 and 4.5, also contributes to its antibacterial properties. Most bacteria thrive in neutral or slightly alkaline environments, and the acidic pH of honey creates an inhospitable environment for bacterial growth. The acidic conditions disrupt bacterial cell membranes and enzymatic functions, further inhibiting microbial proliferation.
4. Presence of Non-Peroxide Bioactive Compounds: In addition to hydrogen peroxide, honey contains a variety of non-peroxide bioactive compounds that contribute to its antibacterial activity. These compounds include phenolic acids, flavonoids, peptides, and other phytochemicals with antimicrobial properties. These bioactive compounds can interfere with bacterial cell metabolism, disrupt cell membranes, and inhibit the synthesis of bacterial proteins and DNA.
5. Antibiotic Resistance Modulation: Another intriguing aspect of honey’s antibacterial activity is its ability to modulate antibiotic resistance in bacteria. Studies have shown that honey can enhance the susceptibility of antibiotic-resistant bacteria to conventional antibiotics, making them more responsive to antimicrobial treatment. This synergistic interaction between honey and antibiotics offers a promising approach for combating antibiotic-resistant infections.
The antibacterial activity of honey is not limited to specific bacterial species but extends to a wide range of pathogenic bacteria, including both Gram-positive and Gram-negative bacteria. Honey is effective against bacteria such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella spp., and Helicobacter pylori, among others. Overall, the multifaceted antibacterial properties of honey make it a valuable natural remedy for treating bacterial infections, wound healing, and promoting overall health and well-being. Its broad-spectrum antimicrobial activity, coupled with its safety, accessibility, and affordability, underscores the potential of honey as an alternative or adjunctive therapy in the fight against bacterial diseases [13]. Further research into the specific mechanisms of action and therapeutic applications of honey’s antibacterial activity is warranted to fully harness its potential in clinical practice and public health initiatives.
Anti-Biofilm Activity of Honey
Biofilms, complex microbial communities encased in a self-produced matrix of extracellular polymeric substances, pose significant challenges in clinical and environmental settings due to their enhanced resistance to antimicrobial agents and immune defenses. Honey demonstrates remarkable efficacy in inhibiting biofilm formation and disrupting pre-formed biofilms across various bacterial species. Its ability to penetrate and disperse biofilm matrices, disrupt bacterial cell-cell communication, and interfere with quorum sensing signaling pathways contributes to its anti-biofilm activity [14]. Moreover, honey’s diverse bioactive components target different stages of biofilm development, including initial attachment, maturation, and dispersal, making it a promising therapeutic agent for biofilm-related infections.
The anti-biofilm activity of honey represents a significant aspect of its therapeutic potential, especially in the context of combating chronic infections and addressing antibiotic resistance. Biofilms are complex microbial communities encased in a self-produced extracellular matrix, adhering to biotic or abiotic surfaces [15]. These biofilms pose a significant challenge in clinical settings due to their enhanced resistance to antimicrobial agents and immune responses. Honey has demonstrated remarkable efficacy in inhibiting biofilm formation and disrupting pre-formed biofilms across a wide range of bacterial species. Several mechanisms contribute to honey’s anti-biofilm activity:
1. Matrix Disruption: Honey can penetrate and disrupt the extracellular matrix of biofilms, which consists of polysaccharides, proteins, and DNA. By degrading the matrix, honey destabilizes the structure of the biofilm, rendering it more susceptible to antimicrobial agents and immune defenses.
2. Interference with Adhesion: Honey inhibits the initial attachment of bacteria to surfaces, preventing the formation of biofilm colonies. The high viscosity of honey and its ability to coat surfaces interfere with bacterial adhesion mechanisms, impeding the establishment of biofilm communities.
3. Quorum Sensing Inhibition: Quorum sensing is a cell-to-cell communication system used by bacteria to coordinate gene expression and regulate biofilm formation. Honey has been shown to interfere with quorum sensing signaling pathways, disrupting the communication between bacteria and inhibiting the expression of genes involved in biofilm development.
4. Antimicrobial Activity: The broad-spectrum antimicrobial activity of honey contributes to its ability to disrupt biofilms. Honey’s antibacterial properties target both planktonic bacteria and bacteria within the biofilm matrix, inhibiting their growth and metabolism.
5. Osmotic Effects: The high sugar content of honey creates a hyperosmotic environment that dehydrates bacterial cells within the biofilm. This osmotic stress disrupts cellular functions and metabolic processes, leading to the inhibition of biofilm formation and the dispersion of pre-existing biofilms.
The anti-biofilm activity of honey has been demonstrated against various pathogenic bacteria, including Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, among others. Honey-based treatments have shown promise in controlling biofilm-related infections, such as chronic wounds, diabetic foot ulcers, urinary tract infections, and respiratory infections [16].
Moreover, honey’s anti-biofilm properties complement its broader therapeutic benefits, including its wound-healing properties, anti-inflammatory effects, and immunomodulatory activities. Honey-based dressings and topical formulations have been utilized in clinical practice to manage biofilm-related wounds and promote tissue repair and regeneration, honey represents a natural and effective strategy for combating biofilm-related infections and addressing the challenges posed by antibiotic-resistant bacteria. Its multifaceted mechanisms of action, including matrix disruption, quorum sensing inhibition, and antimicrobial activity, make it a valuable adjunctive therapy in wound care, infection control, and public health initiatives [17]. Further research into the specific bioactive components and molecular mechanisms underlying honey’s anti-biofilm activity will deepen our understanding of its therapeutic potential and broaden its applications in clinical practice.
Anti-Quorum Sensing Activity of Honey
Quorum sensing is a bacterial cell-cell communication mechanism that regulates the expression of virulence factors, biofilm formation, and microbial pathogenicity in response to population density. Honey has been shown to interfere with quorum-sensing signaling pathways, attenuating the production of quorum-sensing molecules and inhibiting the expression of virulence genes in bacterial pathogens. By disrupting quorum sensing-mediated communication, honey reduces bacterial virulence, impairs biofilm formation, and enhances susceptibility to conventional antibiotics, thereby enhancing the efficacy of antimicrobial treatment strategies [18].
Therapeutic Applications of Honey:
The broad-spectrum antimicrobial activity, anti-biofilm properties, and anti-quorum sensing effects of honey hold promise for various therapeutic applications in clinical medicine, wound management, and the development of novel antimicrobial agents. Honey-based dressings and topical formulations have been successfully utilized in the treatment of acute and chronic wounds, burns, ulcers, and surgical infections. Moreover, honey’s immunomodulatory, anti-inflammatory, and tissue-regenerative properties contribute to its wound-healing capabilities and promote tissue repair and regeneration [19-20]. Furthermore, the synergistic interactions between honey and conventional antibiotics enhance antimicrobial efficacy, overcome antibiotic resistance, and mitigate the emergence of multidrug-resistant pathogens.
Conclusion
In conclusion, honey represents a natural source of potent antimicrobial agents with broad-spectrum activity against bacterial pathogens, biofilms, and quorum sensing-mediated virulence. Its diverse bioactive components, mechanisms of action, and therapeutic applications make it a valuable asset in modern medicine and wound care. The comprehensive review of honey’s antibacterial, anti-biofilm, and anti-quorum sensing properties presented herein underscores its potential as a versatile and effective therapeutic agent for combating microbial infections and addressing the global challenges of antimicrobial resistance. Future research endeavors aimed at elucidating the molecular mechanisms of honey’s antimicrobial activity, optimizing its therapeutic formulations, and exploring its clinical efficacy in diverse medical contexts will further enhance our understanding of its therapeutic potential and broaden its applications in clinical practice.
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