{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T07:51:34Z","timestamp":1768809094507,"version":"3.49.0"},"reference-count":22,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T00:00:00Z","timestamp":1593475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/Multi\/00612\/2013 (CQB)"],"award-info":[{"award-number":["UID\/Multi\/00612\/2013 (CQB)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/DTP\/04567\/2019"],"award-info":[{"award-number":["UID\/DTP\/04567\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The number of cases of failure in the treatment of infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, 7\u03b1-Acetoxy-6\u03b2-hydroxyroyleanone (AHR), a diterpene isolated from different Plectranthus species, showed antibacterial activity, namely against Methicillin-resistant Staphylococcus aureus (MRSA) strains. The high antibacterial activity and low cytotoxicity render this natural compound an interesting alternative against resistant bacteria. The aim of this study is to understand the mechanism of action of AHR on MRSA, using the MRSA\/Vancomycin-intermediate S. aureus (VISA) strain CIP 106760, and to study the AHR effect on lipid bilayers and on the cell wall. Although AHR interacted with lipid bilayers, it did not have a significant effect on membrane passive permeability. Alternatively, bacteria treated with this royleanone displayed cell wall disruption, without revealing cell lysis. In conclusion, the results gathered so far point to a yet undescribed mode of action that needs further investigation.<\/jats:p>","DOI":"10.3390\/biom10070983","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T16:06:54Z","timestamp":1593533214000},"page":"983","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Unveiling the Mechanism of Action of 7\u03b1-acetoxy-6\u03b2-hydroxyroyleanone on an MRSA\/VISA Strain: Membrane and Cell Wall Interactions"],"prefix":"10.3390","volume":"10","author":[{"given":"Filipe","family":"Pereira","sequence":"first","affiliation":[{"name":"Research Center for Biosciences and Health Technologies (CBIOS), Universidade Lus\u00f3fona de Humanidades e Tecnologias, Campo Grande, 376, 1749-024 Lisboa, Portugal"},{"name":"Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcal\u00e1, Campus Universitario, 28871 Alcal\u00e1 de Henares, Spain"}]},{"given":"Teresa","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias da Vida, UCIBIO@REQUIMTE, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2825-149 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9748-7083","authenticated-orcid":false,"given":"Rodrigo F. M.","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"given":"Catarina A. C.","family":"Antunes","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"given":"Catarina","family":"Garcia","sequence":"additional","affiliation":[{"name":"Research Center for Biosciences and Health Technologies (CBIOS), Universidade Lus\u00f3fona de Humanidades e Tecnologias, Campo Grande, 376, 1749-024 Lisboa, Portugal"},{"name":"Department of Biomedical Sciences, Faculty of Pharmacy, University of Alcal\u00e1, Campus Universitario, 28871 Alcal\u00e1 de Henares, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-4031","authenticated-orcid":false,"given":"Catarina P.","family":"Reis","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisboa, Portugal"},{"name":"Institute of Biophysics and Biomedical Bioengeneering (IBEB), Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-5912","authenticated-orcid":false,"given":"Lia","family":"Ascens\u00e3o","sequence":"additional","affiliation":[{"name":"Centro de Estudos do Ambiente e do Mar (CESAM), Faculdade de Ci\u00eancias, Universidade de Lisboa, 1749-016 Lisboa, Portugal"}]},{"given":"Rita G.","family":"Sobral","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias da Vida, UCIBIO@REQUIMTE, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, 2825-149 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7992-8343","authenticated-orcid":false,"given":"Patricia","family":"Rijo","sequence":"additional","affiliation":[{"name":"Research Center for Biosciences and Health Technologies (CBIOS), Universidade Lus\u00f3fona de Humanidades e Tecnologias, Campo Grande, 376, 1749-024 Lisboa, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o do Medicamento (iMed.ULisboa), Faculdade de Farm\u00e1cia, Universidade de Lisboa, 1649-003 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Palacios, L., Rosado, H., Micol, V., Rosato, A.E., Bernal, P., Arroyo, R., Grounds, H., Anderson, J.C., Stabler, R.A., and Taylor, P.W. (2014). Staphylococcal phenotypes induced by naturally occurring and synthetic membrane-interactive polyphenolic \u03b2-lactam resistance modifiers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093830"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/ptr.4961","article-title":"In vitro Antimicrobial Activity of Royleanone Derivatives against Gram-Positive Bacterial Pathogens","volume":"28","author":"Rijo","year":"2014","journal-title":"Phyther. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11101-011-9212-6","article-title":"Recent developments in the bioactivity of mono- and diterpenes: Anticancer and antimicrobial activity","volume":"14","author":"Greay","year":"2015","journal-title":"Phytochem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.2174\/1381612822666151211094521","article-title":"Reactivity of Diterpenoid Quinones: Royleanones","volume":"22","author":"Ladeiras","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.phymed.2005.06.002","article-title":"Abietanes from Plectranthus grandidentatus and P. hereroensis against methicillin- and vancomycin-resistant bacteria","volume":"13","author":"Rijo","year":"2006","journal-title":"Phytomedicine"},{"key":"ref_6","unstructured":"Rijo, P. (2011). Phytochemical Study and Biological Activities of Diterpenes and Derivatives from Plectranthus Species, Universidade De Lisboa Faculdade De Farm\u00e1cia."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1038\/s41598-017-04125-6","article-title":"Development of lysosome-mimicking vesicles to study the effect of abnormal accumulation of sphingosine on membrane properties","volume":"7","author":"Carreira","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6997","DOI":"10.1021\/jp7118229","article-title":"Structural and Dynamic Characterization of the Interaction of the Putative Fusion Peptide of the S2 SARS-CoV Virus Protein with Lipid Membranes","volume":"112","author":"Prieto","year":"2008","journal-title":"J. Phys. Chem. B"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/0003-2697(71)90443-X","article-title":"An accurate and convenient organic phosphorus assay","volume":"39","author":"McClare","year":"1971","journal-title":"Anal. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lakowicz, J.R. (2006). Principles of Fluorescence Spectroscopy, Springer.","DOI":"10.1007\/978-0-387-46312-4"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/mbo3.165","article-title":"The glucosaminidase domain of Atl-the major Staphylococcus aureus autolysin\u2014Has DNA-binding activity","volume":"3","author":"Grilo","year":"2014","journal-title":"Microbiologyopen"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11248","DOI":"10.1016\/S0021-9258(19)49903-1","article-title":"Peptidoglycan composition of a highly methicillin-resistant Staphylococcus aureus strain. The role of penicillin binding protein 2A","volume":"267","author":"Chang","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1128\/JB.188.7.2543-2553.2006","article-title":"Role of murF in Cell Wall Biosynthesis: Isolation and Characterization of a murF Conditional Mutant of Staphylococcus aureus","volume":"188","author":"Sobral","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Figueiredo, T.A., Sobral, R.G., Ludovice, A.M., de Almeida, J.M.F., Bui, N.K., Vollmer, W., de Lencastre, H., and Tomasz, A. (2012). Identification of Genetic Determinants and Enzymes Involved with the Amidation of Glutamic Acid Residues in the Peptidoglycan of Staphylococcus aureus. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002508"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/j.foodcont.2010.02.013","article-title":"Studies on antibacterial activity and antibacterial mechanism of a novel polysaccharide from Streptomyces virginia H03","volume":"21","author":"He","year":"2010","journal-title":"Food Control"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mohammad, H., Reddy, P.V.N., Monteleone, D., Mayhoub, A.S., Cushman, M., Hammac, G.K., and Seleem, M.N. (2015). Antibacterial Characterization of Novel Synthetic Thiazole Compounds against Methicillin-Resistant Staphylococcus pseudintermedius. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130385"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1128\/AAC.00028-06","article-title":"Low-level resistance of Staphylococcus aureus to thrombin-induced platelet microbicidal protein 1 in vitro associated with qacA gene carriage is independent of multidrug efflux pump activity","volume":"50","author":"Bayer","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1186\/s40064-015-1476-7","article-title":"Alteration of Zeta potential and membrane permeability in bacteria: A study with cationic agents","volume":"4","author":"Halder","year":"2015","journal-title":"Springerplus"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.chemphyslip.2012.06.002","article-title":"Biophysical properties of ergosterol-enriched lipid rafts in yeast and tools for their study: Characterization of ergosterol\/phosphatidylcholine membranes with three fluorescent membrane probes","volume":"165","author":"Bastos","year":"2012","journal-title":"Chem. Phys. Lipids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1529\/biophysj.105.066589","article-title":"Direct Visualization of Membrane Leakage Induced by the Antibiotic Peptides: Maculatin, Citropin, and Aurein","volume":"89","author":"Ambroggio","year":"2005","journal-title":"Biophys. J."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gray, D.A., and Wenzel, M. (2020). More than a pore: A current perspective on the in vivo mode of action of the lipopeptide antibiotic daptomycin. Antibiotics, 9.","DOI":"10.3390\/antibiotics9010017"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1089\/mdr.2014.0042","article-title":"Contribution of peptidoglycan amidation to beta-lactam and lysozyme resistance in different genetic lineages of staphylococcus aureus","volume":"20","author":"Figueiredo","year":"2014","journal-title":"Microb. Drug Resist."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/7\/983\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:45:31Z","timestamp":1760175931000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/10\/7\/983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,30]]},"references-count":22,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7]]}},"alternative-id":["biom10070983"],"URL":"https:\/\/doi.org\/10.3390\/biom10070983","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,30]]}}}