{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:54:46Z","timestamp":1768830886099,"version":"3.49.0"},"reference-count":117,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ALiCE","award":["LA\/P\/0045\/2020"],"award-info":[{"award-number":["LA\/P\/0045\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>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 Escherichia coli. 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 \u00b5g\/mL and a minimum bactericidal concentration (MBC) of 512 \u00b5g\/mL. Hydrocinnamic acid had a MIC of 2048 \u00b5g\/mL and an MBC &gt; 2048 \u00b5g\/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 \u03bcg\/mL of chloramphenicol with perillyl alcohol; 0.5 \u03bcg\/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.<\/jats:p>","DOI":"10.3390\/antibiotics12020360","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T02:32:07Z","timestamp":1675909927000},"page":"360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hydrocinnamic Acid and Perillyl Alcohol Potentiate the Action of Antibiotics against Escherichia coli"],"prefix":"10.3390","volume":"12","author":[{"given":"Mariana","family":"Sousa","sequence":"first","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4926-8935","authenticated-orcid":false,"given":"Ana Cristina","family":"Afonso","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"CITAB\u2014Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Tr\u00e1s-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"CEB, LABBELS\u2014Centre of Biological Engineering, Associate Laboratory on Biotechnology and Bioengineering, and Electromechanical Systems, School of Engineering, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-9764","authenticated-orcid":false,"given":"L\u00edlia Soares","family":"Teixeira","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6929-6805","authenticated-orcid":false,"given":"Anabela","family":"Borges","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7492-4965","authenticated-orcid":false,"given":"Maria Jos\u00e9","family":"Saavedra","sequence":"additional","affiliation":[{"name":"CITAB\u2014Centre for the Research and Technology of Agro-Environmental and Biological Sciences, University of Tr\u00e1s-os-Montes e Alto Douro, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4893-1985","authenticated-orcid":false,"given":"L\u00facia Chaves","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"CEB, LABBELS\u2014Centre of Biological Engineering, Associate Laboratory on Biotechnology and Bioengineering, and Electromechanical Systems, School of Engineering, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3355-4398","authenticated-orcid":false,"given":"Manuel","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"LEPABE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, Department of Chemical Engineering, University of Porto, 4200-465 Porto, Portugal"},{"name":"ALiCE\u2014Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, 4200-465 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3934\/microbiol.2018.3.482","article-title":"An Overview of the Antimicrobial Resistance Mechanisms of Bacteria","volume":"4","author":"Reygaert","year":"2018","journal-title":"AIMS Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4137\/PMC.S14459","article-title":"Antibiotics and Bacterial Resistance in the 21st Century","volume":"6","author":"Fair","year":"2014","journal-title":"Perspect. 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