Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against <i>Escherichia coli</i>

The treatment of bacterial infections has been troubled by the increased resistance to antibiotics, instigating the search for new antimicrobial therapies. Phytochemicals have demonstrated broad-spectrum and effective antibacterial effects as well as antibiotic resistance-modifying activity. In this...

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Main Authors: Mariana Sousa, Ana Cristina Afonso, Lília Soares Teixeira, Anabela Borges, Maria José Saavedra, Lúcia Chaves Simões, Manuel Simões
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/12/2/360
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author Mariana Sousa
Ana Cristina Afonso
Lília Soares Teixeira
Anabela Borges
Maria José Saavedra
Lúcia Chaves Simões
Manuel Simões
author_facet Mariana Sousa
Ana Cristina Afonso
Lília Soares Teixeira
Anabela Borges
Maria José Saavedra
Lúcia Chaves Simões
Manuel Simões
author_sort Mariana Sousa
collection DOAJ
description The treatment of bacterial infections has been troubled by the increased resistance to antibiotics, instigating the search for new antimicrobial therapies. Phytochemicals have demonstrated broad-spectrum and effective antibacterial effects as well as antibiotic resistance-modifying activity. In this study, perillyl alcohol and hydrocinnamic acid were characterized for their antimicrobial action against <i>Escherichia coli</i>. Furthermore, dual and triple combinations of these molecules with the antibiotics chloramphenicol and amoxicillin were investigated for the first time. Perillyl alcohol had a minimum inhibitory concentration (MIC) of 256 µg/mL and a minimum bactericidal concentration (MBC) of 512 µg/mL. Hydrocinnamic acid had a MIC of 2048 µg/mL and an MBC > 2048 µg/mL. Checkerboard and time-kill assays demonstrated synergism or additive effects for the dual combinations chloramphenicol/perillyl alcohol, chloramphenicol/hydrocinnamic acid, and amoxicillin/hydrocinnamic acid at low concentrations of both molecules. Combenefit analysis showed synergism for various concentrations of amoxicillin with each phytochemical. Combinations of chloramphenicol with perillyl alcohol and hydrocinnamic acid revealed synergism mainly at low concentrations of antibiotics (up to 2 μg/mL of chloramphenicol with perillyl alcohol; 0.5 μg/mL of chloramphenicol with hydrocinnamic acid). The results highlight the potential of combinatorial therapies for microbial growth control, where phytochemicals can play an important role as potentiators or resistance-modifying agents.
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spelling doaj.art-560369f8e5f442bda3bf67819c4423002023-11-16T18:43:55ZengMDPI AGAntibiotics2079-63822023-02-0112236010.3390/antibiotics12020360Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against <i>Escherichia coli</i>Mariana Sousa0Ana Cristina Afonso1Lília Soares Teixeira2Anabela Borges3Maria José Saavedra4Lúcia Chaves Simões5Manuel Simões6LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, PortugalLEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, PortugalLEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, PortugalLEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, PortugalCITAB—Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Trás-os-Montes e Alto Douro, 5000-801 Vila Real, PortugalCEB, LABBELS—Centre of Biological Engineering, Associate Laboratory on Biotechnology and Bioengineering, and Electromechanical Systems, School of Engineering, University of Minho, 4710-057 Braga, PortugalLEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, PortugalThe treatment of bacterial infections has been troubled by the increased resistance to antibiotics, instigating the search for new antimicrobial therapies. Phytochemicals have demonstrated broad-spectrum and effective antibacterial effects as well as antibiotic resistance-modifying activity. In this study, perillyl alcohol and hydrocinnamic acid were characterized for their antimicrobial action against <i>Escherichia coli</i>. Furthermore, dual and triple combinations of these molecules with the antibiotics chloramphenicol and amoxicillin were investigated for the first time. Perillyl alcohol had a minimum inhibitory concentration (MIC) of 256 µg/mL and a minimum bactericidal concentration (MBC) of 512 µg/mL. Hydrocinnamic acid had a MIC of 2048 µg/mL and an MBC > 2048 µg/mL. Checkerboard and time-kill assays demonstrated synergism or additive effects for the dual combinations chloramphenicol/perillyl alcohol, chloramphenicol/hydrocinnamic acid, and amoxicillin/hydrocinnamic acid at low concentrations of both molecules. Combenefit analysis showed synergism for various concentrations of amoxicillin with each phytochemical. Combinations of chloramphenicol with perillyl alcohol and hydrocinnamic acid revealed synergism mainly at low concentrations of antibiotics (up to 2 μg/mL of chloramphenicol with perillyl alcohol; 0.5 μg/mL of chloramphenicol with hydrocinnamic acid). The results highlight the potential of combinatorial therapies for microbial growth control, where phytochemicals can play an important role as potentiators or resistance-modifying agents.https://www.mdpi.com/2079-6382/12/2/360antibiotic recalcitranceplant-based natural productperillyl alcoholhydrocinnamic acidcombinatorial therapyphytochemical-antibiotic interaction
spellingShingle Mariana Sousa
Ana Cristina Afonso
Lília Soares Teixeira
Anabela Borges
Maria José Saavedra
Lúcia Chaves Simões
Manuel Simões
Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against <i>Escherichia coli</i>
Antibiotics
antibiotic recalcitrance
plant-based natural product
perillyl alcohol
hydrocinnamic acid
combinatorial therapy
phytochemical-antibiotic interaction
title Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against <i>Escherichia coli</i>
title_full Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against <i>Escherichia coli</i>
title_fullStr Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against <i>Escherichia coli</i>
title_full_unstemmed Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against <i>Escherichia coli</i>
title_short Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against <i>Escherichia coli</i>
title_sort hydrocinnamic acid and perillyl alcohol potentiate the action of antibiotics against i escherichia coli i
topic antibiotic recalcitrance
plant-based natural product
perillyl alcohol
hydrocinnamic acid
combinatorial therapy
phytochemical-antibiotic interaction
url https://www.mdpi.com/2079-6382/12/2/360
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