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      Antibacterial effects of vanilla ingredients provide novel treatment options for infections with multidrug-resistant bacteria – A recent literature review

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          Abstract

          Due to the increasing application of antibiotics not only in healthcare settings but also in conventional agriculture and farming, multidrug-resistant (MDR) bacterial pathogens are rising worldwide. Given the increasing prevalence of infections caused by MDR bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species ( ESKAPE pathogen complex), it is pivotal to explore novel alternative or adjunct treatment options such as phytochemicals with antibiotic properties. Vanillin and vanillin acid represent biologically active ingredients in vanilla that has been known for long for its health-beneficial including antimicrobial effects besides its role as flavoring agent. Therefore, we performed a literature search from the past 10 years summarizing the knowledge regarding the effects of vanilla constituents against bacterial including MDR pathogens. Our survey revealed that vanillin and vanillic acid exerted potent effects directed against distinct Gram-positive and Gram-negative bacteria by inhibiting growth, viability, biofilm formation, quorum sensing and virulence. Remarkably, when combining vanillin or vanillic acid with defined synthetic antibiotics pronounced synergistic effects directed against distinct pathogenic including ESCAPE strains could be observed. In conclusion, vanilla ingredients constitute promising alternative or adjunct options in the combat of infections caused by MDR bacterial pathogens.

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          Most cited references43

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          Global trends in antimicrobial use in food animals.

          Demand for animal protein for human consumption is rising globally at an unprecedented rate. Modern animal production practices are associated with regular use of antimicrobials, potentially increasing selection pressure on bacteria to become resistant. Despite the significant potential consequences for antimicrobial resistance, there has been no quantitative measurement of global antimicrobial consumption by livestock. We address this gap by using Bayesian statistical models combining maps of livestock densities, economic projections of demand for meat products, and current estimates of antimicrobial consumption in high-income countries to map antimicrobial use in food animals for 2010 and 2030. We estimate that the global average annual consumption of antimicrobials per kilogram of animal produced was 45 mg⋅kg(-1), 148 mg⋅kg(-1), and 172 mg⋅kg(-1) for cattle, chicken, and pigs, respectively. Starting from this baseline, we estimate that between 2010 and 2030, the global consumption of antimicrobials will increase by 67%, from 63,151 ± 1,560 tons to 105,596 ± 3,605 tons. Up to a third of the increase in consumption in livestock between 2010 and 2030 is imputable to shifting production practices in middle-income countries where extensive farming systems will be replaced by large-scale intensive farming operations that routinely use antimicrobials in subtherapeutic doses. For Brazil, Russia, India, China, and South Africa, the increase in antimicrobial consumption will be 99%, up to seven times the projected population growth in this group of countries. Better understanding of the consequences of the uninhibited growth in veterinary antimicrobial consumption is needed to assess its potential effects on animal and human health.
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            Mechanisms of Antibiotic Resistance.

            Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic "attack" is the prime example of bacterial adaptation and the pinnacle of evolution. "Survival of the fittest" is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material, or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and to devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.
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              Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies

              Pseudomonas aeruginosa is an opportunistic pathogen that is a leading cause of morbidity and mortality in cystic fibrosis patients and immunocompromised individuals. Eradication of P. aeruginosa has become increasingly difficult due to its remarkable capacity to resist antibiotics. Strains of Pseudomonas aeruginosa are known to utilize their high levels of intrinsic and acquired resistance mechanisms to counter most antibiotics. In addition, adaptive antibiotic resistance of P. aeruginosa is a recently characterized mechanism, which includes biofilm-mediated resistance and formation of multidrug-tolerant persister cells, and is responsible for recalcitrance and relapse of infections. The discovery and development of alternative therapeutic strategies that present novel avenues against P. aeruginosa infections are increasingly demanded and gaining more and more attention. Although mostly at the preclinical stages, many recent studies have reported several innovative therapeutic technologies that have demonstrated pronounced effectiveness in fighting against drug-resistant P. aeruginosa strains. This review highlights the mechanisms of antibiotic resistance in P. aeruginosa and discusses the current state of some novel therapeutic approaches for treatment of P. aeruginosa infections that can be further explored in clinical practice.
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                Author and article information

                Contributors
                Journal
                Eur J Microbiol Immunol (Bp)
                Eur J Microbiol Immunol (Bp)
                EUJMI
                European Journal of Microbiology & Immunology
                Akadémiai Kiadó (Budapest )
                2062-509X
                2062-8633
                23 September 2022
                September 2022
                September 2022
                : 12
                : 3
                : 53-62
                Affiliations
                [1] Gastrointestinal Microbiology Research Group, Institute of Microbiology, Infectious Diseases and Immunology, Charité - University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health , Berlin, Germany
                Author notes
                [* ]Corresponding author. Charité - University Medicine Berlin, CC5, Institute of Microbiology, Infectious Diseases and Immunology, Campus Benjamin Franklin, FEM , Garystr. 5, D-14195 Berlin, Germany. Tel.: +49-30-450524318. E-mail: markus.heimesaat@ 123456charite.de
                Author information
                https://orcid.org/0000-0001-6399-651X
                Article
                10.1556/1886.2022.00015
                9530676
                36149764
                47c0e5fe-5237-45ff-bcad-b813f522e2ae
                © 2022 The Author(s)

                Open Access. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and reproduction in any medium for non-commercial purposes, provided the original author and source are credited, a link to the CC License is provided, and changes – if any – are indicated.

                History
                : 03 August 2022
                : 07 September 2022
                Page count
                Tables: 1, Equations: 2, References: 44, Pages: 10
                Categories
                Article

                vanillin,vanillic acid,phenolic compounds,phytochemicals,natural products,synergistic antimicrobial effects,antibiotic enhancers,novel antimicrobial therapies,multidrug-resistant (mdr) bacteria,escape pathogens

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