Bacteria of the genus Staphylococcus are important human and veterinary pathogens. A crucial characteristic for this group of bacteria is that they can easily acquire mechanisms of antibiotic resistance for a plethora of antibiotics currently in use for human and animal therapies. Therefore, there is a great need to find novel, non-antibiotic chemotherapeutics with marked antistaphylococcal activity. Promising but still underestimated group of potential antistaphylococcal chemotherapeutics constitute bee products: honey, pollen, royal jelly, fermented pollen and especially propolis. Another group of natural products that exhibit promising antibacterial activity is essential oils. Usefulness of bee products and essential oils in the treatment of infections caused by S. aureus has been confirmed by results of many investigations carried out by researches in different regions of the world. In this chapter, we have presented the review of publication in this area as well as perspectives and limitations of future applications of these two groups of natural products.
- Staphylococcus aureus
- bee products
- fermented pollen
- essential oils
1.1. Staphylococci: important human and veterinary pathogens
Staphylococci also belong to the most important animal pathogens. Infections caused by these bacteria leads to huge economic losses in agriculture and food industry. Contamination of food products by these bacteria is a serious issue due to their completely lack of susceptibility to lysozyme and very low susceptibility to nisin, two important agents used as preservatives in food industry [17, 18].
1.2. Natural products as potential antimicrobial agents
All presented above aspects (the prevalence of the staphylococci in the environment, their high virulence potential and first of all rapid increase in antibiotic resistance) clearly indicate that there is an urgent need to develop new, effective inexpensive and not covered by current existing mechanisms of resistance antistaphylococcal agents. Interesting groups of antimicrobials, which meet all these expectations and could be used for treatment of
The main purpose of the preparation of this chapter is to demonstrate that bee and plant products are still interesting and promising group of antimicrobials. Their antibacterial activity is not only a matter of history from the pre-antibiotic era. Their large antimicrobial potential was confirmed with modern microbiological methods and analytical techniques and is well-documented in many scientific publications.
2. Antimicrobial activity of bee products
2.1.1. Basic information and mechanisms of antimicrobial activity
From ancient times, honey was a very valued component of the diet. This is mainly due to its characteristic sweet taste. The main uses of honey are as follows: as a spread on bread, a sweetener for tea, milk and coffee, for preparing desserts and cakes. Recently, it has been also proposed to use honey as a component of healthy, high energetic, beverages. The sweet taste of honey is apparent from its chemical composition. Sugars, mainly fructose and glucose, and minor amounts of oligosaccharides account for about 80% of its weight. The centuries of observations have also shown that regular consumption of honey is beneficial to the health of consumer. Therefore, this product was widely used as drug in traditional medicine, one of the most important except of herbs. The research carried out during several last decades finally confirmed that honey (and also other bee products) is a beneficial agent in treatment of a wide spectrum of human diseases, such as some cardiovascular and gastrointestinal tract disorders, infections within upper respiratory tract including cough, as well as in healing of infected wounds . While folk medicine was based only on tradition and experience, the achievements of modern science and medicine have found confirmation of the therapeutic potential of honey, as the consequence of its chemical composition. It has been revealed that crucial for therapeutic properties of honey are its non-sugar components such as: enzymes, peptides, free amino acids, vitamins, organic acids, flavonoids, phenolic acids and other phytochemicals, minerals . Especially interesting subject seems to be its antimicrobial activity. As it was mentioned above, this product was successfully used in treatment of skin and soft tissue infections and for elimination of pathogens infecting mucosal of respiratory tract. In all these situations, physical contact of honey (its components) with infected tissue (microorganisms infecting the tissue) is possible. The antimicrobial action of honey is based on several mechanisms: the acidity (low pH, usually in the range from 3.4 to 6.1), osmotic pressure of sugars present in honey and the presence of bacteriostatic and bactericidal substances such as H2O2, antioxidants, lysozyme, polyphenols, phenolic acids, flavonoids, methylglyoxal and bee peptides [21–24]. The crucial component that is responsible for the antimicrobial activity of majority of the honey types is hydrogen peroxide, which is formed as a side product of the oxidation of glucose by glucose oxidase—the enzyme which is introduced to the honey from the salivary glands of bees. Interestingly glucose oxidase is inactive in non-diluted honey . The inhibition of growth of bacteria in honey, at the original concentration of this product, is mainly caused by high concentration of sugars (high osmotic pressure) coupled with high acidity [21, 22]. Therefore, it can be stored for long period of time (at least 2 years) without any additional treatment or supplementation with preservatives. When honey is diluted to certain extent, its antibacterial activity is shifted from osmotic- and pH-dependent to peroxide-dependent mechanism of action based on the generation of H2O2 . This scenario takes place when honey is used for treatment of infections, e.g. infected wound. On the basis of current state of knowledge, it can be said that other mentioned above components of honey, mainly phytochemicals, seem to only support the antibacterial effect of generated H2O2. The dominant role of the enzyme in the antimicrobial activity of several polish unifloral honeys was recently confirmed in the researches that were carried out in our group. Preincubation of honeys solutions in 80°C for only 10 min resulted in complete loss of antibacterial activity of all tested honeys. The same effect was observed when suspensions of tested bacterial cells in solutions of honeys were supplemented with catalase. In both cases the observed, complete losses of activity of honeys were the consequence of lack of possibilities for H2O2 generation. Heat treatment resulted in denaturation of the enzyme, and in the presence of catalase, the generated hydrogen peroxide was immediately decomposed . On the other hand, antimicrobial activity of honey also depends on the botanical source which was used by bees to collect the nectar. Buckwheat, thyme and cornflower honeys usually exhibit high antimicrobial activity, whilst produced in Poland in large amounts rape honey do not affect the growth of neither Gram-positive nor Gram-negative bacteria [27, 28]. Thus, the types of phytochemicals as well their concentration is important for final antimicrobial potential of honey. The issue of role of phytochemicals in the antimicrobial potential of honey is still not clear and is a subject of many interesting research. Hydrogen peroxide is also a known cytostatic agent; however, its concentration in honey is on a very low level which is safe for humans and animals. According to Lusby et al. , the concentration of H2O2 in honey is thousand times lower than in the common 3% antiseptic solution available in pharmacies; however, its constant production causes prolonged activity which can be considered as an advantage. The concentration of hydrogen peroxide on a non-toxic and stable level is probably regulated by antioxidants and pollen-derived catalase which destroy excess amounts of H2O2 .
2.1.2. Honey as a potential antistaphylococcal agent
The results of many investigations, carried out in different geographical regions of the world, revealed especially high efficiency of honey in treatment of infections caused by Gram-positive microorganisms, e.g. staphylococci. The mentioned above investigation carried out in our group revealed that honeys obtained from some species of plants, namely cornflower (
2.1.3. Perspectives and limitations of treatment staphylococcal infections with honey
From the point of view of possibilities of exploiting of the therapeutic potential of honey especially promising, and most realistic, seem to be application of this product as a component of wound dressing materials. Using honey to eliminate pathogens from infected wounds has a long tradition, which can be counted in hundred or even thousands of years. Currently, several companies specialize in production of dressings containing honey. However, many technical problems still have to be solved: (1) elimination of indigenous flora of honey, especially spores, without thermal or chemical treatment—results in deactivation of glucose oxidase and loss of antimicrobial activity, (2) inhibition of natural process of crystallization of honey, (3) large diversity of antimicrobial activity of honey—only the honeys with certified antibacterial activities should be used for medical applications. These problems could be partly solved by using manuka honey. However, research of many investigators revealed that many “classical honeys”—which activity is based mainly on the generation of hydrogen peroxide, exhibit even higher activity in comparison to manuka honey with a high content of methylglyoxal—550 mg/L [27, 28, 33]. Thus, they are also good candidates to be used in clinical practice as a component of dressings, ointments and creams, or direct application on the surface of infected skin, sores, diabetic foot, or mucous, e.g. in the oral cavity or genital tract.
2.2.1. Basic information
The bees collect four products: nectar and honeydew for production of honey (source of carbohydrates), pollen (source of proteins) and propolis. Propolis is not a component of bees’ diet; however, it is absolutely necessary for the proper development of bee colonies. This product, which is also called bee glue, is a natural resinous substance produced from plants’ buds and exudates, modified by addition of bees’ salivary secretions and wax. Similarly, as in the case of honey, propolis is a product of complex chemical composition. Some of its ingredients mainly polyphenols and flavonoids exhibit high antimicrobial activity. As a consequence, it is used as a hive disinfectant. Bees use propolis for elimination of pathogenic microorganisms from the walls of hive and cells of honeycomb, in which larvae develop (nest wells) and honey is stored . It is important for prevention of development of such dangerous pathogens as
2.2.2. Possibilities of application of propolis in therapy of bacterial infections
Similarly to honey, propolis was widely used in traditional medicine. The detailed history of using propolis in medicine and a discussion of perspectives of its future application have been recently presented by Silva-Carvalho and coworkers . The chemical composition of this product depends on many factors: the geographical region where it was collected (the species of plants which were available for bees), season, weather conditions and many other. Some significant correlations were found primarily in the case of chemical composition of propolis and place of its isolation. On this basis, several different types of propolis have been proposed, e.g. poplar propolis, birch, green, red, “Pacific” and “Canarian”. This classification still evaluates and new, different types of propolis are being recognized, e.g. Mediterranean or Portuguese . At least, 13 different types of propolis have been identified in Brazil . Because of differences in chemical composition the biological, including antibacterial, activity of different propolis samples may vary significantly. However, the carried out to date studies revealed that staphylococci and other Gram-positive bacteria are usually highly sensitive to this product collected in many different geographical locations. Propolis remains especially popular in the non-conventional medicine in Brazil as well as in other tropical countries, thus the product obtained in this region is well-characterized. The global market size of propolis was about 2300 tons in 2015 (it is established that it will increase to 2900 tons in 2021), and Brazil is the largest production and exporting country of this product (https://www.whatech.com/market-research/materials-chemicals/125806-world-propolis-industry-trends-share-size-2021-forecast-report). High anti-staphylococcal activity of propolis sourced from State of Paraná, in Brazil, was observed by Pamplona-Zomenhan and coworkers, the MIC50 and MIC90 for the 210 strains (162 MSSA and 48 MRSA) were both 1420 μg/mL . The results of investigations performed by the groups of Fidoralisi  and Santana  indicated that propolis extracts might be effective against mastitis-causing
Due to its health-promoting properties, propolis is widely used as a component of cosmetics, some food and beverages. In our opinion, these applications are not adequate to the biological properties of this product. The results of many presented above studies clearly indicate that propolis is a promising antimicrobial agent. Moreover, many other biological activities of this product have been described, including antioxidant, antiviral, antitumor, antifungal and immunomodulatory properties . Large diversity of its chemical composition and consequently its biological activity eliminate propolis from clinical applications. Nevertheless, this limitation should be considered in therapy of serious, life-threatening infections (or other diseases), where the exact amount of biological active agent has to be used.
2.2.3. Other bee products: pollen and royal jelly
Investigation of antimicrobial activity of pollen, fermented pollen (bee bread) and royal jelly is not as popular as in the case of honey and propolis. However, several authors confirmed that these products also reveal some antimicrobial potential. Boukraa and coworkers revealed that MIC value for royal jelly against
Antimicrobial, antimutagenic, antioxidant and even anti-inflammatory activity of bee pollen (collected in Portugal and Spain) has been revealed in the research of Pascola and colleagues , and
2.2.4. Honey and other bee products as a source of bacteriocinogenic bacteria with bactericidal antistaphylococcal activity
However, bacteriocins are usually active against bacteria closely related to producing strain, but there are also many exceptions to this general rule, e.g. nisin, which is active against broad spectrum of Gram-positive bacteria . Recently carried out research of the group of Prof. Worobo from Cornell University revealed that honey should be considered as a potential source of microorganisms producing promising antimicrobial compounds, especially bacteriocins . The mentioned authors analyzed two Manuka honeys from New Zealand and six domestic honeys from US. The 2217 isolates out of 2398 strains (92.5%) exhibited activity at least against one of the tested microorganisms. Among all the bacterial indicator strains,
However, results of some successful investigations have been published the trials of isolation of bacteriocinogenic bacterial strains from honey and other than honeybee products were rarely carried out to date. In our opinion, especially, promising source of bacteria producing interesting bacteriocins could be fermented pollen—it is pollen which is collected by bees for the winter and early spring. The high antimicrobial activity of fermented pollen is the consequence of lactic acid bacteria (LAB) presence in this product, and the products of LAB metabolism—lactic acid, as well as bacteriocins.
3. Antibacterial activity of essential oils and plant extracts against
Essential oils (EO) and their components are becoming increasingly popular as antimicrobial agents. They belong to the group of secondary metabolites that are enriched in compounds based on an isoprene structure and are called terpenes. They occur as di-, tri-, tetra-, hemi- and sesquiterpenes. The compounds that contain additional elements, usually oxygen, are termed terpenoids. Terpenes, terpenoids, as well as essential oils containing these substances exhibit antibacterial activity against broad spectrum of microorganisms including staphylococci .
One of the best characterized EO, which effectively inhibits growth of
Promising results were also obtained in the investigation of antimicrobial potential of lavender oil (LO). The oil obtained from
Another interesting, from the point of view of its antimicrobial properties, is Thymus essential oils (TOs). Its main chemical components are α-thujone, α-pinene, camphene, β-pinene, p-cymene, α-terpinene, linalool, borneol, β-caryophyllene, thymol and carvacrol . Different chemotypes of the essential oil from the genus
Recently research of many authors showed also the antimicrobial activity of geranium oil (GO) against MRSA [84, 85]. Among 67 components of geranium oil from
The antibacterial activity of essential oils from oregano (
Essential oil of cinnamon and cinnamaldehyde, which is main chemical constituent of this oil, also showed activity against MRSA. Essential oil from
The number of research on antibacterial properties of extracts from medicinal plants against MRSA increased in recent years. These researches are conducted in different countries and show that extracts of plants are rich source of unique phytochemicals with activity against MRSA. Among recently investigated plant was
According to research of Endo and Dias Filho , MRSA is also sensitive to berberine (plant alkaloid) which is used in Chinese medicine. MICs values of berberine ranged from 62.5 to 250 μg/mL and MBC values were the same or twofold above the MIC. Highly potent anti-MRSA activity with MIC values in range of 25–50 mg/mL was detected among Libyan medicinal plants such as
Staphylococci belong to the most important pathogens for both humans and animals. The number of antibiotics effective in treatment of infections caused by these pathogenic bacteria is rapidly decreasing. Many centuries of observation and the use of bee products and essential oils in folk medicine as well as the results of advanced scientific research carried out during the last several decades clearly confirm high antimicrobial, including antistaphylococcal activity of these products. We have no doubt that they are an interesting and promising alternative to classical antibiotics and should be more seriously considered as therapeutic agents.
Preparing the chapter was supported by the Grant no 2015/18/E/NZ6/00700 from the “National Science Centre, Poland”.
The authors are also grateful to Dr. Marta Schilemann for her help in preparing the English version of the manuscript of the chapter.
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