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      Honey: Another Alternative in the Fight against Antibiotic-Resistant Bacteria?

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          Abstract

          Antibacterial resistance has become a challenging situation worldwide. The increasing emergence of multidrug-resistant pathogens stresses the need for developing alternative or complementary antimicrobial strategies, which has led the scientific community to study substances, formulas or active ingredients used before the antibiotic era. Honey has been traditionally used not only as a food, but also with therapeutic purposes, especially for the topical treatment of chronic-infected wounds. The intrinsic characteristics and the complex composition of honey, in which different substances with antimicrobial properties are included, make it an antimicrobial agent with multiple and different target sites in the fight against bacteria. This, together with the difficulty to develop honey-resistance, indicates that it could become an effective alternative in the treatment of antibiotic-resistant bacteria, against which honey has already shown to be effective. Despite all of these assets, honey possesses some limitations, and has to fulfill a number of requirements in order to be used for medical purposes.

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          Most cited references126

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          Antimicrobial activity of flavonoids

          Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (−)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2′-trihydroxy-5′-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.
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            Antimicrobial resistance: a global multifaceted phenomenon.

            Antimicrobial resistance (AMR) is one of the most serious global public health threats in this century. The first World Health Organization (WHO) Global report on surveillance of AMR, published in April 2014, collected for the first time data from national and international surveillance networks, showing the extent of this phenomenon in many parts of the world and also the presence of large gaps in the existing surveillance. In this review, we focus on antibacterial resistance (ABR), which represents at the moment the major problem, both for the high rates of resistance observed in bacteria that cause common infections and for the complexity of the consequences of ABR. We describe the health and economic impact of ABR, the principal risk factors for its emergence and, in particular, we illustrate the highlights of four antibiotic-resistant pathogens of global concern - Staphylococcus aureus, Klebsiella pneumoniae, non-typhoidal Salmonella and Mycobacterium tuberculosis - for whom we report resistance data worldwide. Measures to control the emergence and the spread of ABR are presented.
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              Recent advances in understanding the antibacterial properties of flavonoids.

              Antibiotic resistance is a major global problem and there is a pressing need to develop new therapeutic agents. Flavonoids are a family of plant-derived compounds with potentially exploitable activities, including direct antibacterial activity, synergism with antibiotics, and suppression of bacterial virulence. In this review, recent advances towards understanding these properties are described. Information is presented on the ten most potently antibacterial flavonoids as well as the five most synergistic flavonoid-antibiotic combinations tested in the last 6 years (identified from PubMed and ScienceDirect). Top of these respective lists are panduratin A, with minimum inhibitory concentrations (MICs) of 0.06-2.0 μg/mL against Staphylococcus aureus, and epicatechin gallate, which reduces oxacillin MICs as much as 512-fold. Research seeking to improve such activity and understand structure-activity relationships is discussed. Proposed mechanisms of action are also discussed. In addition to direct and synergistic activities, flavonoids inhibit a number of bacterial virulence factors, including quorum-sensing signal receptors, enzymes and toxins. Evidence of these molecular effects at the cellular level include in vitro inhibition of biofilm formation, inhibition of bacterial attachment to host ligands, and neutralisation of toxicity towards cultured human cells. In vivo evidence of disruption of bacterial pathogenesis includes demonstrated efficacy against Helicobacter pylori infection and S. aureus α-toxin intoxication. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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                Author and article information

                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                04 November 2020
                November 2020
                : 9
                : 11
                : 774
                Affiliations
                [1 ]Department of Food Hygiene and Technology, Faculty of Veterinary Science, University of León, Campus de Vegazana, 24071 León, Spain; pcomf@ 123456unileon.es (P.C.-F.); jmfreb@ 123456unileon.es (J.M.F.); metorr@ 123456unileon.es (M.E.T.)
                [2 ]Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; mmestevinho@ 123456med.up.pt
                [3 ]Department of Onco-Hematology, Portuguese Institute of Oncology of Porto (IPO-Porto), 4200-072 Porto, Portugal; mario.sousa.pimenta@ 123456ipoporto.min-saude.pt
                [4 ]Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, 5300-252 Bragança, Portugal
                Author notes
                [* ]Correspondence: leticia@ 123456ipb.pt ; Tel.: +351-273303342
                Author information
                https://orcid.org/0000-0001-5170-3687
                https://orcid.org/0000-0002-3438-0852
                Article
                antibiotics-09-00774
                10.3390/antibiotics9110774
                7694208
                33158063
                f4c824c4-f85d-4a4a-9a87-79ff02f562ac
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 October 2020
                : 02 November 2020
                Categories
                Review

                natural antibiotic,antimicrobial compounds,antibacterial action mechanisms,medical uses,honey-resistance,honey limitations

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