{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:06:41Z","timestamp":1791223601203,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council (NSERC)","doi-asserted-by":"publisher","award":["CRDPJ 448052"],"award-info":[{"award-number":["CRDPJ 448052"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Island Abbey Foods","award":["CRDPJ 448052"],"award-info":[{"award-number":["CRDPJ 448052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Carvacrol, a mono-terpenoid phenol found in herbs, such as oregano and thyme, has excellent antibacterial properties against Streptococcus pyogenes. However, its mechanism of bactericidal activity on S. pyogenes has not been elucidated. Objectives: This study investigated the bactericidal mechanism of carvacrol using three strains of S. pyogenes. Methods: Flow cytometry (FCM) experiments were conducted to determine carvacrol\u2019s membrane permeabilization and cytoplasmic membrane depolarization activities. Protoplasts of S. pyogenes were used to investigate carvacrol\u2019s effects on the membrane, followed by gel electrophoresis. The carvacrol-treated protoplasts were examined by transmission electron microscopy (TEM) to observe ultrastructural morphological changes. The fluidity of the cell membrane was measured by steady-state fluorescence anisotropy. Thin-layer chromatographic (TLC) profiling was conducted to study the affinity of carvacrol for membrane phospholipids. Results: Increased membrane permeability and decreased membrane potential from FCM and electron microscopy observations revealed that carvacrol killed the bacteria primarily by disrupting membrane integrity, leading to whole-cell lysis. Ultra-structural morphological changes in the membrane induced by carvacrol over a short period were confirmed using the S. pyogenes protoplast and membrane isolate models in vitro. In addition, changes in the other biophysical properties of the bacterial membrane, including concentration- and time-dependent increased fluidity, were observed. TLC experiments showed that carvacrol preferentially interacts with membrane phosphatidylglycerol (P.G.), phosphatidylethanolamine (P.E.), and cardiolipins (CL). Conclusions: Carvacrol exhibited rapid bactericidal action against S. pyogenes by disrupting the bacterial membrane and increasing permeability, possibly due to affinity with specific membrane phospholipids, such as P.E., P.G., and CL. Therefore, the bactericidal concentration of carvacrol (250 \u00b5g\/mL) could be used to develop safe and efficacious natural health products for managing streptococcal pharyngitis or therapeutic applications.<\/jats:p>","DOI":"10.3390\/pharmaceutics14101992","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T05:33:14Z","timestamp":1663824794000},"page":"1992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Bactericidal Activity of Carvacrol against Streptococcus pyogenes Involves Alteration of Membrane Fluidity and Integrity through Interaction with Membrane Phospholipids"],"prefix":"10.3390","volume":"14","author":[{"given":"Niluni M.","family":"Wijesundara","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science, Dalhousie University, Halifax, NS B3H 3E2, Canada"},{"name":"Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada"},{"name":"Department of Animal Science, Faculty of Animal Science and Export Agriculture, Uva Wellassa University, Badulla 90000, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song F.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada"},{"name":"Department of Applied Oral Sciences, Faculty of Dentistry, Dalhousie University, Halifax, NS B3H 3E2, Canada"},{"name":"Canadian Center for Vaccinology, Dalhousie University, Nova Scotia Health Authority, and the Izaak Walton Killam Health Centre, Halifax, NS B3H 3E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7240-9126","authenticated-orcid":false,"given":"Zhenyu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada"},{"name":"Canadian Center for Vaccinology, Dalhousie University, Nova Scotia Health Authority, and the Izaak Walton Killam Health Centre, Halifax, NS B3H 3E2, Canada"},{"name":"Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada"},{"name":"Laboratory Medicine, Division of Microbiology at the Queen Elizabeth II Health Sciences Centre, Nova Scotia Health Authority, Halifax, NS B3H 1V8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9592-3075","authenticated-orcid":false,"given":"David N.","family":"Langelaan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-0052","authenticated-orcid":false,"given":"H. P. Vasantha","family":"Rupasinghe","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, Dalhousie University, Halifax, NS B3H 3E2, Canada"},{"name":"Department of Plant, Food, and Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada"},{"name":"Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 3E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.micpath.2018.02.026","article-title":"Essential oils from Origanum vulgare and Salvia officinalis exhibit antibacterial and anti-biofilm activities against Streptococcus pyogenes","volume":"117","author":"Wijesundara","year":"2018","journal-title":"Microb. 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