Honey Bee Products as an Alternative or Complement to Classical Antibiotics – 2nd Edition

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 59053

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Guest Editor
Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, Poland
Interests: bacteria and yeast drug resistance; staphylococcus aureus; Candida spp.; bee products; essential oils; peptidoglycan hydrolases
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Special Issue Information

Dear Colleagues,

For some years now, we have been witnessing with concern the arrival of the post-antibiotic era. The resistance of pathogenic bacteria and fungi to well-known antibiotics and synthetic chemotherapeutics is becoming a major global healthcare challenge. Therefore, there is a great need to find novel, non-antibiotic chemotherapeutics with marked antibacterial/antifungal activity.

Bee products, including honey, propolis, royal jelly, pollen, and fermented pollen-bee bread, constitute a promising but still underestimated group of potential antimicrobial chemotherapeutics. For centuries, bee honey and propolis comprised the most important raw materials of folk medicine. They were successfully used in the treatment of a wide array of human diseases, including infections (mainly within the upper respiratory tract and chronic wounds). In contrast to many other popular traditional medicines, the achievements of modern medicine confirm the diverse therapeutic potential of bee products, which is a consequence of their chemical composition. The outcomes of several studies also confirmed the synergistic interaction of propolis with classical antibiotics and synthetic chemotherapeutics. As in the case of the first edition of this Special Issue, manuscripts presenting all aspects of the possible application of bee products (and the chemical ingredients in these products) for the treatment of bacterial or fungal infections are welcome.

The link to the first edition: https://www.mdpi.com/journal/antibiotics/special_issues/honey_

Dr. Piotr Szweda
Guest Editor

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Keywords

  • bacteria and fungi drug resistance
  • honey
  • propolis
  • royal jelly
  • pollen
  • bee bread
  • bee products
  • polyphenols
  • Bacillus
  • lactic acid bacteria

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Related Special Issue

Published Papers (11 papers)

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Research

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32 pages, 3536 KiB  
Article
Antimicrobial Evaluation of Various Honey Types against Carbapenemase-Producing Gram-Negative Clinical Isolates
by Elisavet Stavropoulou, Chrysoula (Chrysa) Voidarou, Georgios Rozos, Natalia Vaou, Michael Bardanis, Theodoros Konstantinidis, Georgia Vrioni and Athanasios Tsakris
Antibiotics 2022, 11(3), 422; https://doi.org/10.3390/antibiotics11030422 - 21 Mar 2022
Cited by 13 | Viewed by 4265
Abstract
The development of antibiotic resistance is a major public health issue, as infections are increasingly unresponsive to antibiotics. Emerging antimicrobial resistance has raised researchers’ interest in the development of alternative strategies using natural compounds with antibacterial activity, like honey, which has emerged as [...] Read more.
The development of antibiotic resistance is a major public health issue, as infections are increasingly unresponsive to antibiotics. Emerging antimicrobial resistance has raised researchers’ interest in the development of alternative strategies using natural compounds with antibacterial activity, like honey, which has emerged as an agent to treat several infections and wound injuries. Nevertheless, the antibacterial effect of honey was mostly evaluated against Gram-positive bacteria. Hence, the objective of our study was to evaluate the antibacterial activity, as well as the physicochemical parameters, of genuine Greek honeys against multidrug-resistant Gram-negative pathogenic bacteria. In this vein, we aimed to study the in vitro antibacterial potential of rare Greek honeys against Verona integron-encoded metallo-β-lactamase (VIM)- or Klebsiella pneumoniae carbapenemase-producing multidrug-resistant Gram-negative pathogens. Physicochemical parameters such as pH, hydrogen peroxide, free acidity, lactonic acid, total phenols total flavonoids, free radical scavenging activities, tyrosinase enzyme inhibitory activity and kojic acid were examined. Moreover, the antimicrobial activity of 10 different honey types was evaluated in five consecutive dilutions (75%, 50%, 25%, 12.5% and 6.25%) against the clinical isolates by the well diffusion method, as well as by the determination of the minimum inhibition concentration after the addition of catalase and protease. Almost all the physicochemical parameters varied significantly among the different honeys. Fir and manuka honey showed the highest values in pH and H2O2, while the free acidity and lactonic acid levels were higher in chestnut honey. Total phenols, total flavonoids and free radical scavenging activities were found higher in cotton, arbutus and manuka honey, and finally, manuka and oregano honeys showed higher tyrosinase inhibition activity and kojic acid levels. The antimicrobial susceptibility depended on the type of honey, on its dilution, on the treatment methodology and on the microorganism. Arbutus honey was the most potent against VIM-producing Enterobacter cloacae subsp. dissolvens in 75% concentration, while fir honey was more lethal for the same microorganism in the 25% concentration. Many honeys outperformed manuka honey in their antibacterial potency. It is of interest that, for any given concentration in the well diffusion method and for any given type of honey, significant differences were not detected among the four multidrug-resistant pathogens, which explains that the damaging effect to the bacterial cells was the same regardless of the bacterial species or strain. Although the antimicrobial potency of different honey varieties dependents on their geographical origin and on their compositional differences, the exact underlying mechanism remains yet unclear. Full article
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13 pages, 2269 KiB  
Article
Combined Inhibitory Effect of Fir (Abies alba Mill.) Honeydew Honey and Probiotic Bacteria Lactiplantibacillus plantarum on the Growth of Salmonella enterica Serotype Typhimurium
by Silvestar Mežnarić, Irena Brčić Karačonji, Goranka Crnković, Andrija Lesar, Tomislav Pavlešić, Darinka Vučković and Ivana Gobin
Antibiotics 2022, 11(2), 145; https://doi.org/10.3390/antibiotics11020145 - 24 Jan 2022
Cited by 5 | Viewed by 3083
Abstract
Honey is a natural food consisting mainly of sugars, enzymes, amino acids, organic acids, vitamins, minerals and aromatic substances. In addition to specific organoleptic properties, honey also has other components that contribute to its nutritional and health value. Proteins, vitamins, minerals, organic acids [...] Read more.
Honey is a natural food consisting mainly of sugars, enzymes, amino acids, organic acids, vitamins, minerals and aromatic substances. In addition to specific organoleptic properties, honey also has other components that contribute to its nutritional and health value. Proteins, vitamins, minerals, organic acids and phenolic compounds, the most variable components of honey, are predominantly responsible for its strong bioactive effect. Honeydew honey is a less known type of honey with outstanding antimicrobial and antioxidant properties that also demonstrates prebiotic effects and can promote the growth of probiotic bacteria. Foodborne illnesses can be prevented by using probiotic strains in combination with prebiotics. The aim of this study was for the first time to determine potential synergistic antimicrobial effect of fir (Abies alba Mill.) honeydew honey (HS) and probiotic bacteria Lactiplantibacillus plantarum on Salmonella enterica serotype Typhimurium, a primary cause of foodborne illnesses. The effect of three different samples of fir honeydew honey on the growth of L. plantarum in de Man, Rogosa and Sharpe (MRS) medium and the potential synergistic effect of HSs and L. plantarum on the growth of S. Typhimurium in the Brain Heart Infusion (BHI) medium were examined. The results indicate that concentrations of 1 and 5% of all three HS samples stimulate the growth and metabolic activity of L. plantarum, while a concentration of 10% inhibits the growth of L. plantarum. The concentration of 5% of all three HS and L. plantarum combined inhibits the growth of S. Typhimurium in BHI broth. Fir honeydew honey showed potential prebiotic properties and antimicrobial activity, both of which can synergistically enhance the probiotic efficacy of L. plantarum against S. Typhimurium To conclude, the combination of fir honeydew honey and L. plantarum represents a successful combination against S. Typhimurium and additional experiments are necessary regarding the mechanisms of their combined effect. Full article
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16 pages, 3311 KiB  
Article
Chemical, Cytotoxic, and Anti-Inflammatory Assessment of Honey Bee Venom from Apis mellifera intermissa
by Iouraouine El Mehdi, Soraia I. Falcão, Mustapha Harandou, Saïd Boujraf, Ricardo C. Calhelha, Isabel C. F. R. Ferreira, Ofélia Anjos, Maria G. Campos and Miguel Vilas-Boas
Antibiotics 2021, 10(12), 1514; https://doi.org/10.3390/antibiotics10121514 - 10 Dec 2021
Cited by 8 | Viewed by 3966
Abstract
The venom from Apis mellifera intermissa, the main honey bee prevailing in Morocco, has been scarcely studied, despite its known potential for pharmacological applications. In the present work, we investigated the composition, the anti-inflammatory activity, and the venom’s cytotoxic properties from fifteen [...] Read more.
The venom from Apis mellifera intermissa, the main honey bee prevailing in Morocco, has been scarcely studied, despite its known potential for pharmacological applications. In the present work, we investigated the composition, the anti-inflammatory activity, and the venom’s cytotoxic properties from fifteen honey bee venom (HBV) samples collected in three regions: northeast, central, and southern Morocco. The chemical assessment of honey bee venom was performed using LC-DAD/ESI/MSn, NIR spectroscopy and AAS spectroscopy. The antiproliferative effect was evaluated using human tumor cell lines, including breast adenocarcinoma, non-small cell lung carcinoma, cervical carcinoma, hepatocellular carcinoma, and malignant melanoma. Likewise, we assessed the anti-inflammatory activity using the murine macrophage cell line. The study provides information on the honey bee venom subspecies’ main components, such as melittin, apamin, and phospholipase A2, with compositional variation depending on the region of collection. Contents of toxic elements such as cadmium, chromium, and plumb were detected at a concentration below 5 ppm, which can be regarded as safe for pharmaceutical use. The data presented contribute to the first study in HBV from Apis mellifera intermissa and highlight the remarkable antiproliferative and anti-inflammatory effects of HBV, suggesting it to be a candidate natural medicine to explore. Full article
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12 pages, 1627 KiB  
Article
A Specific Mixture of Propolis and Carnosic Acid Triggers a Strong Fungicidal Action against Cryptococcus neoformans
by Alejandra Argüelles, Ruth Sánchez-Fresneda, Elisa Martínez-Mármol, José Antonio Lozano, Francisco Solano and Juan Carlos Argüelles
Antibiotics 2021, 10(11), 1395; https://doi.org/10.3390/antibiotics10111395 - 13 Nov 2021
Cited by 5 | Viewed by 2049
Abstract
Current antifungal chemotherapy against the prevalent basidiomycete Cryptococcus neoformans displays some drawbacks. This pathogenic fungus is refractory to echinocandins, whereas conventional treatment with amphotericin B plus 5-fluorocytosine has a limited efficacy. In this study, we explored the potential cryptococcal activity of some natural [...] Read more.
Current antifungal chemotherapy against the prevalent basidiomycete Cryptococcus neoformans displays some drawbacks. This pathogenic fungus is refractory to echinocandins, whereas conventional treatment with amphotericin B plus 5-fluorocytosine has a limited efficacy. In this study, we explored the potential cryptococcal activity of some natural agents. After conducting a screening test with a set of propolis from different geographical areas, we selected an extract from China, which displayed a certain cytotoxic activity against C. neoformans, due to this extract being cheap and easily available in large amounts. The combination of this kind of propolis with carnosic acid in a 1:4 ratio induced a stronger fungicidal effect, which occurred following a synergistic pattern, without visible alterations in external cell morphology. Furthermore, several carnosic acid–propolis formulations applied onto preformed biofilms decreased the metabolic activity of the sessile cells forming biofilms. These data support the potential application of mixtures containing these two natural extracts in the design of new antifungal strategies in order to combat opportunistic infections caused by prevalent pathogenic fungi. Full article
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13 pages, 1510 KiB  
Article
Application of Heating on the Antioxidant and Antibacterial Properties of Malaysian and Australian Stingless Bee Honey
by Nurul Ainaa Farhanah Mat Ramlan, Aina Syahirah Md Zin, Nur Fatihah Safari, Kim Wei Chan and Norhasnida Zawawi
Antibiotics 2021, 10(11), 1365; https://doi.org/10.3390/antibiotics10111365 - 8 Nov 2021
Cited by 14 | Viewed by 3327
Abstract
In the honey industry, heat treatments are usually applied to maintain honey’s quality and shelf life. Heat treatment is used to avoid crystallisation and allow the easy use of honey, but treatment with heat might affect the antioxidant and antibacterial activities, which are [...] Read more.
In the honey industry, heat treatments are usually applied to maintain honey’s quality and shelf life. Heat treatment is used to avoid crystallisation and allow the easy use of honey, but treatment with heat might affect the antioxidant and antibacterial activities, which are the immediate health effects of honey. This study will determine the effect of heat treatment on Malaysian and Australian stingless bee honey (SBH) produced by the common bee species in both countries. Eighteen honey samples were subjected to heat at 45 °C, 55 °C and 65 °C for one hour and subsequently analysed for their total phenolic content (TPC), total flavonoid content (TFC), DPPH radical scavenging activity, ferric reducing antioxidant power (FRAP) and minimum inhibitory concentration (MIC). The results show that all samples had high TPC, TFC and antioxidant activities before the treatment. The heat treatments did not affect (p < 0.05) the TPC, TFC and antioxidant activities in most samples, but did inhibit the antibacterial activities consistently in most of the samples, regardless of the bee species and country of origin. This study also confirms a strong correlation between TPC and TFC with FRAP activities for the non-heated and heated honey samples (p < 0.05). Other heat-sensitive bioactive compounds in SBH should be measured to control the antibacterial properties present. Full article
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15 pages, 3135 KiB  
Article
Effects of the Carbohydrate Sources Nectar, Sucrose and Invert Sugar on Antibacterial Activity of Honey and Bee-Processed Syrups
by Veronika Bugarova, Jana Godocikova, Marcela Bucekova, Robert Brodschneider and Juraj Majtan
Antibiotics 2021, 10(8), 985; https://doi.org/10.3390/antibiotics10080985 - 15 Aug 2021
Cited by 14 | Viewed by 5235
Abstract
Honey is a functional food with health-promoting properties. Some types of honey are used in wound care for the treatment of acute and chronic infected wounds. Increased interest in using honey as a functional food and as a base for wound care products [...] Read more.
Honey is a functional food with health-promoting properties. Some types of honey are used in wound care for the treatment of acute and chronic infected wounds. Increased interest in using honey as a functional food and as a base for wound care products causes limited availability of raw honey. Numerous studies suggest that the protein content of honey is mainly comprised of bee-derived proteins and peptides, with a pronounced antibacterial effect. Therefore, the aim of our study was to characterize for the first time the antibacterial activity of raw honeys and bee-processed syrups which were made by processing sucrose solution or invert sugar syrup in bee colonies under field conditions. Furthermore, we compared the contents of glucose oxidase (GOX) and the levels of hydrogen peroxide (H2O2) in honey samples and bee-processed syrups. These parameters were also compared between the processed sucrose solution and the processed invert sugar syrup. Our results clearly show that natural honey samples possess significantly higher antibacterial activity compared to bee-processed syrups. However, no differences in GOX contents and accumulated levels of H2O2 were found between honeys and bee-processed syrups. Comparison of the same parameters between bee-processed feeds based on the two artificial carbohydrate sources revealed no differences in all measured parameters, except for the content of GOX. The amount of GOX was significantly higher in bee-processed sucrose solutions, suggesting that processor bees can secrete a higher portion of carbohydrate metabolism enzymes. Determination of honey color intensity showed that in bee colonies, bee-processed syrups were partially mixed with natural honey. Further research is needed to identify the key botanical compounds in honey responsible for the increased antibacterial potential of honey. Full article
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14 pages, 2830 KiB  
Article
Medical-Grade Honey as an Alternative Treatment for Antibiotics in Non-Healing Wounds—A Prospective Case Series
by Adéla Holubová, Lucie Chlupáčová, Lada Cetlová, Niels A. J. Cremers and Andrea Pokorná
Antibiotics 2021, 10(8), 918; https://doi.org/10.3390/antibiotics10080918 - 28 Jul 2021
Cited by 17 | Viewed by 6632
Abstract
Non-healing wounds are usually colonised by various types of bacteria. An alternative to antibiotic treatment in patients with infected wounds with local signs of inflammation may be medical-grade honey (MGH), which favourably affects the healing process with its antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory [...] Read more.
Non-healing wounds are usually colonised by various types of bacteria. An alternative to antibiotic treatment in patients with infected wounds with local signs of inflammation may be medical-grade honey (MGH), which favourably affects the healing process with its antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory properties. The objective of this study was to evaluate the effect of MGH therapy on the healing process of non-healing wounds of various aetiologies and different wound colonisations. Prospective, observation–intervention case studies (n = 9) of patients with wounds of various aetiologies (venous leg ulcers, diabetic foot ulcers, surgical wound dehiscence) are presented. All wounds were treated with MGH and the healing trajectory was rigorously and objectively monitored. In all cases, pain, odour, and exudation were quickly resolved, which led to an improvement in the quality of life of patients. Despite the proven bacterial microflora in wounds, antibiotic treatment was not necessary. The effects of MGH alleviated the signs of local infection until their complete elimination. In eight out of nine cases, the non-healing wound was completely healed. MGH has antimicrobial, anti-inflammatory, and antioxidant effects in wounds of various aetiologies and forms an effective alternative for the use of antibiotics for treating locally infected wounds. Full article
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14 pages, 1259 KiB  
Article
Bee Pollen and Bee Bread as a Source of Bacteria Producing Antimicrobials
by Karolina Pełka, Randy W. Worobo, Justyna Walkusz and Piotr Szweda
Antibiotics 2021, 10(6), 713; https://doi.org/10.3390/antibiotics10060713 - 13 Jun 2021
Cited by 20 | Viewed by 3943
Abstract
The principal objective of the study was the isolation and identification of bacteria that are present in mature bee bread (BB) and dried (ready for selling and consumption) bee pollen (BP). Obtained isolates were screened for their potential to inhibit select human pathogenic [...] Read more.
The principal objective of the study was the isolation and identification of bacteria that are present in mature bee bread (BB) and dried (ready for selling and consumption) bee pollen (BP). Obtained isolates were screened for their potential to inhibit select human pathogenic bacteria and their ability to produce enzymes of particular industrial importance. Four and five samples of BP and BB, respectively, were used for the study. In total, 81 strains of bacteria were isolated, and 34 (42%) of them exhibited antagonistic interactions with at least one reference strain of pathogenic bacteria, namely Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 29213, Staphylococcus epidermidis 12228, Pseudomonas aeruginosa ATCC 27857, and Escherichia coli ATCC 25922. The sequencing of the 16S rRNA gene revealed that all strains producing antimicrobials belong to the genus Bacillus spp., and among them, five species were identified: B. pumilus (n = 17), B. altitudinis (n = 9), B. licheniformis (n = 4), B. subtilis (n = 2), and B. safensis (n = 1). Furthermore, 69, 54, 39, and 29 of the strains exhibited lipolytic, proteolytic, cellulolytic, and esterolytic activity, respectively. Alpha amylase and beta galactosidase activity were rarely observed, and none of the strains produced laccase. The outcomes of the study revealed that BP and BB can be considered potential sources of bacteria producing antimicrobial agents and/or enzymes of particular industrial importance. Of course, additional research is required to verify this hypothesis, but the results of preliminary studies are promising. Full article
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16 pages, 726 KiB  
Article
Biological Properties of Bee Bread Collected from Apiaries Located across Greece
by Nikos Asoutis Didaras, Ioannis Kafantaris, Tilemachos G. Dimitriou, Chrysanthi Mitsagga, Katerina Karatasou, Ioannis Giavasis, Dimitris Stagos, Grigoris D. Amoutzias, Fani Hatjina and Dimitris Mossialos
Antibiotics 2021, 10(5), 555; https://doi.org/10.3390/antibiotics10050555 - 10 May 2021
Cited by 23 | Viewed by 3649
Abstract
Bee bread is the only fermented product of the beehive. It constitutes the main source of proteins, lipids, vitamins, and macro- and microelements in honeybee nutrition and it exerts antioxidant and antimicrobial properties, though research on these aspects has been limited so far. [...] Read more.
Bee bread is the only fermented product of the beehive. It constitutes the main source of proteins, lipids, vitamins, and macro- and microelements in honeybee nutrition and it exerts antioxidant and antimicrobial properties, though research on these aspects has been limited so far. In this study 18 samples of Greek bee bread, two of which were monofloral, were collected during different seasons from diverse locations such as Crete and Mount Athos and were tested for their bioactivity. Samples were analyzed for their antibacterial properties, antioxidant activity, total phenolic content (TPC), and total flavonoid content (TFC). The antimicrobial activity of each sample was tested against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Salmonella typhimurium. Our data demonstrate that all samples exert inhibitory and most of them bactericidal activity against at least two pathogens. Furthermore, all samples exert significant antioxidant activity, where the monofloral Castanea Sativa sample demonstrated superior antioxidant activity. Nevertheless, the antioxidant and antimicrobial activity were not strongly correlated. Furthermore, machine learning methods demonstrated that the palynological composition of the samples is a good predictor of their TPC and ABTS activity. This is the first study that focuses on the biological properties of Greek bee bread and demonstrates that bee bread can be considered a functional food and a possible source of novel antimicrobial compounds. Full article
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Review

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39 pages, 1554 KiB  
Review
Bee Bread as a Promising Source of Bioactive Molecules and Functional Properties: An Up-To-Date Review
by Meryem Bakour, Hassan Laaroussi, Driss Ousaaid, Asmae El Ghouizi, Imane Es-Safi, Hamza Mechchate and Badiaa Lyoussi
Antibiotics 2022, 11(2), 203; https://doi.org/10.3390/antibiotics11020203 - 5 Feb 2022
Cited by 39 | Viewed by 8096
Abstract
Bee bread is a natural product obtained from the fermentation of bee pollen mixed with bee saliva and flower nectar inside the honeycomb cells of a hive. Bee bread is considered a functional product, having several nutritional virtues and various bioactive molecules with [...] Read more.
Bee bread is a natural product obtained from the fermentation of bee pollen mixed with bee saliva and flower nectar inside the honeycomb cells of a hive. Bee bread is considered a functional product, having several nutritional virtues and various bioactive molecules with curative or preventive effects. This paper aims to review current knowledge regarding the chemical composition and medicinal properties of bee bread, evaluated in vitro and in vivo, and to highlight the benefits of the diet supplementation of bee bread for human health. Bee bread extracts (distilled water, ethanol, methanol, diethyl ether, and ethyl acetate) have been proven to have antioxidant, antifungal, antibacterial, and antitumoral activities, and they can also inhibit α-amylase and angiotensin I-converting enzyme in vitro. More than 300 compounds have been identified in bee bread from different countries around the world, such as free amino acids, sugars, fatty acids, minerals, organic acids, polyphenols, and vitamins. In vivo studies have revealed the efficiency of bee bread in relieving several pathological cases, such as hyperglycemia, hyperlipidemia, inflammation, and oxidative stress. Full article
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31 pages, 1783 KiB  
Review
Honey as an Ecological Reservoir of Antibacterial Compounds Produced by Antagonistic Microbial Interactions in Plant Nectars, Honey and Honey Bee
by Katrina Brudzynski
Antibiotics 2021, 10(5), 551; https://doi.org/10.3390/antibiotics10050551 - 9 May 2021
Cited by 50 | Viewed by 13056
Abstract
The fundamental feature of “active honeys” is the presence and concentration of antibacterial compounds. Currently identified compounds and factors have been described in several review papers without broader interpretation or links to the processes for their formation. In this review, we indicate that the [...] Read more.
The fundamental feature of “active honeys” is the presence and concentration of antibacterial compounds. Currently identified compounds and factors have been described in several review papers without broader interpretation or links to the processes for their formation. In this review, we indicate that the dynamic, antagonistic/competitive microbe–microbe and microbe–host interactions are the main source of antibacterial compounds in honey. The microbial colonization of nectar, bees and honey is at the center of these interactions that in consequence produce a range of defence molecules in each of these niches. The products of the microbial interference and exploitive competitions include antimicrobial peptides, antibiotics, surfactants, inhibitors of biofilm formation and quorum sensing. Their accumulation in honey by horizontal transfer might explain honey broad-spectrum, pleiotropic, antibacterial activity. We conclude that honey is an ecological reservoir of antibacterial compounds produced by antagonistic microbial interactions in plant nectars, honey and honey bee. Thus, refocusing research on secondary metabolites resulting from these microbial interactions might lead to discovery of new antibacterial compounds in honey that are target-specific, i.e., acting on specific cellular components or inhibiting the essential cellular function. Full article
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