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      Antimycobacterial Activity of Cinnamaldehyde in a Mycobacterium tuberculosis(H37Ra) Model

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          Abstract

          The purpose of the study was to evaluate the antimycobacterial activity and the possible action mode of cinnamon bark essential oil and its main constituent—cinnamaldehyde—against the Mycobacterium tuberculosis ATCC 25177 strain. Cinnamaldehyde was proved to be the main bioactive compound responsible for mycobacterial growth inhibition and bactericidal effects. The antimycobacterial activity of cinnamaldehyde was found to be comparable with that of ethambutol, one of the first-line anti-TB antibiotics. The selectivity index determined using cell culture studies in vitro showed a high biological potential of cinnamaldehyde. In M. tuberculosis cells exposed to cinnamaldehyde the cell membrane stress sensing and envelope preserving system are activated. Overexpression of clgR gene indicates a threat to the stability of the cell membrane and suggests a possible mechanism of action. No synergism was detected with the basic set of antibiotics used in tuberculosis treatment: ethambutol, isoniazid, streptomycin, rifampicin, and ciprofloxacin.

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          Mechanisms of antibacterial action of three monoterpenes.

          Domenico Trombetta, Francesco Castelli, Maria Sarpietro … (2005)
          In the present paper, we report the antimicrobial efficacy of three monoterpenes [linalyl acetate, (+)menthol, and thymol] against the gram-positive bacterium Staphylococcus aureus and the gram-negative bacterium Escherichia coli. For a better understanding of their mechanisms of action, the capability of these three monoterpenes to damage biomembranes was evaluated by monitoring the release, following exposure to the compounds under study, of the water-soluble fluorescent marker carboxyfluorescein from unilamellar vesicles with different lipidic compositions (phosphatidylcholine, phosphatidylcholine/phosphatidylserine [9:1], phosphatidylcholine/stearylamine [9:1], and phosphatidylglycerol/cardiolipin [9:1]). Furthermore, the interaction of the terpenes tested with dimyristoylphosphatidylcholine multilamellar vesicles as model membranes was monitored by means of differential scanning calorimetry. Finally, the results were related to the relative lipophilicity and water solubility of the compounds examined. Taken together, our findings lead us to speculate that the antimicrobial effect of (+)menthol, thymol, and linalyl acetate may result, at least partially, from a perturbation of the lipid fraction of microorganism plasma membrane, resulting in alterations of membrane permeability and in leakage of intracellular materials. Besides being related to physicochemical characteristics of the drugs (such as lipophilicity and water solubility), this effect seems to be dependent on lipid composition and net surface charge of microbial membranes. Furthermore, the drugs might cross the cell membranes, penetrating into the interior of the cell and interacting with intracellular sites critical for antibacterial activity.
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            Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis.

            J.-C. Palomino, A MARTÍN, M. Camacho … (2002)
            A method for detecting multidrug-resistant Mycobacterium tuberculosis by using a reduction of resazurin is described. Eighty clinical isolates were evaluated against isoniazid and rifampin; results at 7 days were compared with those of the proportion method. Specificity and sensitivity were excellent. The method is simple, inexpensive, and rapid and might be used with other antituberculosis drugs.
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              Antibacterial activity of Thymus maroccanus and Thymus broussonetii essential oils against nosocomial infection - bacteria and their synergistic potential with antibiotics.

              Mariam Fadli, Asmaa Saad, Sami Sayadi … (2012)
              The aim of this study was to evaluate the antibacterial effect of the association between conventional antibiotics and essential oils (EOs) of endemic Moroccan thyme species, Thymus maroccanus and T. broussonetii, on antibiotic-resistant bacteria involved in nosocomial infections. Synergistic interactions between antibiotics (ciprofloxacin, gentamicin, pristinamycin, and cefixime) and EOs, and between T. maroccanus and T. Broussonetii EOs were determined by the checkerboard test. Serial dilutions of two antimicrobial agents were mixed together so that each row (and column) contained a fixed amount of the first agent and increasing amounts of the second one. The results indicate that the oils had a high inhibitory activity against tested bacteria, except for Pseudomonas aeruginosa. In parallel with the increase of cellular killing, the release of 260nm-absorbing materials from bacterial cells, treated with EOs, increased in response to oil concentration. Out of 80 combinations tested between EOs and antibiotics, 71% showed total synergism, 20% had partial synergistic interaction and 9% showed no effect. Combination with carvacrol, the major constituent of T. maroccanus and T. broussonetii, showed also an interesting synergistic effect in combination with ciprofloxacin. The effect on Gram-positive bacteria was more important than on Gram-negative bacteria. These findings are very promising since the use of these combinations for nosocomial infections treatment is likely to reduce the minimum effective dose of the antibiotics, thus minimizing their possible toxic side effects and treatment cost. However, further investigations are needed to assess the potential for therapeutic application. Copyright © 2011 Elsevier GmbH. All rights reserved.
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                Author and article information

                Contributors
                Simone Carradori: Role: Academic Editor
                Maria Daglia: Role: Academic Editor
                Annabella Vitalone: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 18 September 2018
                Publication date Collection: September 2018
                Volume: 23
                Issue: 9
                Electronic Location Identifier: 2381
                Affiliations
                [1 ]Chair and Department of Biochemistry and Biotechnology, Medical University of Lublin, Chodzki 1, PL-20093 Lublin, Poland; joanna.golus@ 123456umlub.pl (J.G.); agata.przekora@ 123456umlub.pl (A.P.); g.ginalska@ 123456umlub.pl (G.G.)
                [2 ]Medical Plant Unit, Chair and Department of Pharmacognosy, Medical University of Lublin, Chodzki 1, PL-20093 Lublin, Poland; agnieszka.ludwiczuk@ 123456umlub.pl (A.L.); elwira.sieniawska@ 123456umlub.pl (E.S.)
                Author notes
                [* ]Correspondence: rafal.sawicki@ 123456umlub.pl ; Tel.: +48-60631-2059
                Author information
                https://orcid.org/0000-0002-6593-8484
                https://orcid.org/0000-0003-1108-613X
                https://orcid.org/0000-0003-4773-0329
                Article
                Publisher ID: molecules-23-02381
                DOI: 10.3390/molecules23092381
                PMC ID: 6225461
                PubMed ID: 30231479
                SO-VID: f17c1c9e-0ce3-4167-a095-0cee9cbe2a2a
                Copyright © © 2018 by the authors.
                License:

                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
                Date received : 20 August 2018
                Date accepted : 16 September 2018
                Categories
                Subject: Article

                Keywords: selectivity index,synergy,cell membrane,stress sensing,clgr expression
                Data availability:
                Keywords: selectivity index, synergy, cell membrane, stress sensing, clgr expression

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