{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:47:37Z","timestamp":1782362857995,"version":"3.54.5"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Background: Candida albicans is the main etiological agent of oral candidiasis and expresses several virulence-associated traits that contribute to tissue invasion and persistence within the host. Among these, morphogenesis and hydrolytic enzyme secretion are central to fungal pathogenicity. Carvacrol, a phenolic monoterpenoid found in essential oils from aromatic plants, has demonstrated antifungal activity against Candida species, although its effects on virulence phenotypes in clinical isolates remain poorly explored. Therefore, this study investigated the effects of carvacrol on morphogenesis and lipase activity in clinical isolates of C. albicans obtained from oral candidiasis. Methods: Thirteen clinical isolates of C. albicans obtained from the oral mucosa of patients with oral candidiasis and one reference strain (ATCC 90028) were evaluated in the presence and absence of carvacrol (256 \u03bcg\/mL). The effects of carvacrol on germ tube formation, morphology index, hyphal length, colony filamentation in Spider medium, and lipase activity were analyzed using phenotypic assays. Results: Carvacrol reduced germ tube formation in most of the evaluated strains and decreased the overall morphology index, indicating attenuation of filamentous morphologies. In strains that maintained hyphal growth, treatment with carvacrol significantly reduced hyphal length. In addition, colonies grown in Spider medium supplemented with carvacrol exhibited predominantly smooth morphologies, with reduced filamentous formation. Lipase activity was also inhibited in all evaluated strains in the presence of the compound. Notably, variability in phenotypic response was observed among clinical isolates, particularly in strain 97, which maintained partial filamentation under treatment conditions. Conclusions: Exposure to carvacrol was associated with alterations in morphogenesis- and lipase-associated phenotypes in clinical isolates of C. albicans under inhibitory conditions. Because the experiments were conducted using a concentration corresponding to 2\u00d7 MIC, the present findings do not allow discrimination between specific modulation of virulence-associated phenotypes and indirect effects associated with growth inhibition.<\/jats:p>","DOI":"10.3390\/jof12070462","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T03:20:21Z","timestamp":1782357621000},"page":"462","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Carvacrol on Morphogenesis and Lipase-Associated Phenotypes in Clinical Isolates of Candida albicans"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2620-1869","authenticated-orcid":false,"given":"Iasmin Freitas Pimentel","family":"Pequeno","sequence":"first","affiliation":[{"name":"Clinical Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5073-7033","authenticated-orcid":false,"given":"Larissa Alves","family":"da Silva","sequence":"additional","affiliation":[{"name":"Clinical Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luanna","family":"de Oliveira e Lima","sequence":"additional","affiliation":[{"name":"Clinical Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1734-1177","authenticated-orcid":false,"given":"Meryellem Bezerra","family":"Soares","sequence":"additional","affiliation":[{"name":"Clinical Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Mendes","family":"Soares","sequence":"additional","affiliation":[{"name":"Clinical Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimundo Euz\u00e9bio","family":"da Costa Neto","sequence":"additional","affiliation":[{"name":"Clinical Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9567-4096","authenticated-orcid":false,"given":"Jos\u00e9 Maria","family":"Barbosa Filho","sequence":"additional","affiliation":[{"name":"Pharmaceutical Technology Laboratory, Department of Pharmaceutical Sciences, Federal University of Para\u00edba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-4821","authenticated-orcid":false,"given":"Felipe Queiroga Sarmento","family":"Guerra","sequence":"additional","affiliation":[{"name":"Clinical Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme Maranh\u00e3o","family":"Chaves","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Mycology, DMIC\u2014Department of Mycology\u2014BC, Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walicyranison Pl\u00ednio","family":"da Silva Rocha","sequence":"additional","affiliation":[{"name":"Clinical Mycology Laboratory, Department of Pharmaceutical Sciences, Federal University of Paraiba, Jo\u00e3o Pessoa 58051-900, Para\u00edba, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.4103\/0973-029X.141325","article-title":"Oral candidiasis: An overview","volume":"18","author":"Singh","year":"2014","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/21505594.2021.2019950","article-title":"Pathogenesis and virulence of Candida albicans","volume":"13","author":"Lopes","year":"2022","journal-title":"Virulence"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Vila, T., Sultan, A.S., Montelongo-Jauregui, D., and Jabra-Rizk, M.A. (2020). Oral candidiasis: A disease of opportunity. J. Fungi, 6.","DOI":"10.3390\/jof6010015"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103575","DOI":"10.1016\/j.micpath.2019.103575","article-title":"Characterization of oral candidiasis and the Candida species profile in patients with oral mucosal diseases","volume":"134","author":"Hu","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.clindermatol.2016.02.022","article-title":"Oral candidiasis","volume":"34","author":"Millsop","year":"2016","journal-title":"Clin. Dermatol."},{"key":"ref_6","unstructured":"Taylor, M., Brizuela, M., and Raja, A. (2024). Oral Candidiasis. StatPearls, StatPearls Publishing."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Karajacob, A.S., Azizan, N.B., Al-Maleki, A.R.M., Goh, J.P.E., Loke, M.F., Khor, H.M., Ho, G.F., Ponnampalavanar, S., and Tay, S.T. (2023). Candida species and oral mycobiota of patients clinically diagnosed with oral thrush. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0284043"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mroczynska, M., and Brillowska-Dabrowska, A. (2021). Virulence of clinical Candida isolates. Pathogens, 10.","DOI":"10.3390\/pathogens10040466"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yoo, Y.J., Kim, A.R., Perinpanayagam, H., Han, S.H., and Kum, K.Y. (2020). Candida albicans virulence factors and pathogenicity for endodontic infections. Microorganisms, 8.","DOI":"10.3390\/microorganisms8091300"},{"key":"ref_10","first-page":"415","article-title":"Effect of some plant extract against virulence factors of Candida albicans isolated from UTI patients","volume":"18","author":"Mejbel","year":"2018","journal-title":"Biochem. Cell Arch."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Abirami, G., Alexpandi, R., Durgadevi, R., Kannappan, A., and Veera Ravi, A. (2020). Inhibitory effect of Morin against Candida albicans pathogenicity and virulence factor production: An in vitro and in vivo approach. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.561298"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xie, Y., Hua, H., and Zhou, P. (2022). Magnolol as a potent antifungal agent inhibits Candida albicans virulence factors via the PKC and Cek1 MAPK signaling pathways. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.935322"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mukaremera, L., Lee, K.K., Mora-Montes, H.M., and Gow, N.A.R. (2017). Candida albicans yeast, pseudohyphal, and hyphal morphogenesis differentially affects immune recognition. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00629"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Priya, A., and Pandian, S.K. (2020). Piperine impedes biofilm formation and hyphal morphogenesis of Candida albicans. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00756"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ciurea, C.N., Kosovski, I.B., Mare, A.D., Toma, F., Pintea-Simon, I.A., and Man, A. (2020). Candida and candidiasis\u2014Opportunism versus pathogenicity: A review of the virulence traits. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060857"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Silva-Rocha, W.P., de Azevedo, M.F., Ferreira, M.R.A., da Silva, J.d.F., Svidzinski, T.I., Milan, E.P., Soares, L.A., Rocha, K.B., Uch\u00f4a, A.F., and Mendes-Giannini, M.J. (2017). Effect of the ethyl acetate fraction of Eugenia uniflora on proteins global expression during morphogenesis in Candida albicans. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.01788"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1976273","DOI":"10.1155\/2017\/1976273","article-title":"Experimental germ tube induction in Candida albicans: An evaluation of the effect of sodium bicarbonate on morphogenesis and comparison with pooled human serum","volume":"2017","author":"Matare","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"73","DOI":"10.7883\/yoken.JJID.2006.73","article-title":"Comparison of proteinase, lipase and alpha-glucosidase activities from the clinical isolates of Candida species","volume":"59","author":"Bramono","year":"2006","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_19","first-page":"107","article-title":"Candida lipases: A review on biochemical, molecular and pathogenic aspects","volume":"76","author":"Castillo","year":"2019","journal-title":"Rev. Fac. Cienc. Medicas"},{"key":"ref_20","first-page":"e172","article-title":"Therapeutic tools for oral candidiasis: Current and new antifungal drugs","volume":"24","author":"Sevillano","year":"2019","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_21","first-page":"100","article-title":"Antifungal activity of essential oils against Candida spp.","volume":"3","author":"Butzge","year":"2020","journal-title":"Braz. J. Health Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1021\/acs.chemrev.0c00199","article-title":"Antifungal drug resistance: Molecular mechanisms in Candida albicans and beyond","volume":"121","author":"Lee","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_23","first-page":"113","article-title":"Antifungal activity of carvacrol on ergosterol synthesis in multidrug-resistant Candida albicans","volume":"22","author":"Khodavandi","year":"2018","journal-title":"Hamdan Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kaskatepe, B., Aslan, E.S., Ozturk, S., Safi, O.Z., Subasi, E., Koyuncu, M., Vlainic, J., and Kosalec, I. (2022). Antifungal and anti-virulent activity of Origanum majorana L. essential oil on Candida albicans and in vivo toxicity in the Galleria mellonella larval model. Molecules, 27.","DOI":"10.3390\/molecules27030663"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1128\/AAC.00551-15","article-title":"The monoterpene carvacrol generates endoplasmic reticulum stress in the pathogenic fungus Candida albicans","volume":"59","author":"Chaillot","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s11030-017-9787-y","article-title":"Perspectives on medicinal properties of natural phenolic monoterpenoids and their hybrids","volume":"22","author":"Rajput","year":"2018","journal-title":"Mol. Divers."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Niu, C., Wang, C., Yang, Y., Chen, R., Zhang, J., Chen, H., Zhuge, Y., Li, J., Cheng, J., and Xu, K. (2020). Carvacrol induces Candida albicans apoptosis associated with Ca2+\/Calcineurin pathway. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00192"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.ijantimicag.2008.01.028","article-title":"In vitro activity of terpenes against Candida biofilms","volume":"31","author":"Dalleau","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1080\/08927014.2012.749398","article-title":"Terpenoids of plant origin inhibit morphogenesis, adhesion, and biofilm formation by Candida albicans","volume":"29","author":"Raut","year":"2013","journal-title":"Biofouling"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"da Silva-Rocha, W.P., Lemos, V.L., Svidzinski, T.I., Milan, E.P., and Chaves, G.M. (2014). Candida species distribution, genotyping and virulence factors of Candida albicans isolated from the oral cavity of kidney transplant recipients of two geographic regions of Brazil. BMC Oral Health, 14.","DOI":"10.1186\/1472-6831-14-20"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1128\/jcm.34.2.454-456.1996","article-title":"Direct identification and recognition of yeast species from clinical material by using Albicans ID and CHROMagar Candida plates","volume":"34","author":"Baumgartner","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"ref_32","unstructured":"Murray, P.R. (1995). Candida, Cryptococcus and other yeasts of medical importance. Manual of Clinical Microbiology, ASM Press."},{"key":"ref_33","first-page":"3143","article-title":"A morphology index for characterization of cell shape in Candida albicans","volume":"135","author":"Odds","year":"1989","journal-title":"J. Gen. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1099\/00221287-146-8-1881","article-title":"Survival in experimental Candida albicans infections depends on inoculum growth conditions as well as animal host","volume":"146","author":"Odds","year":"2000","journal-title":"Microbiology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Silva-Rocha, W.P., de Brito Lemos, V.L., Ferreira, M.R.A., Soares, L.A.L., Svidzisnki, T.I.E., Milan, E.P., and Chaves, G.M. (2015). Effect of the crude extract of Eugenia uniflora in morphogenesis and secretion of hydrolytic enzymes in Candida albicans from the oral cavity of kidney transplant recipients. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0522-x"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1439-0507.1997.tb00186.x","article-title":"Extracellular enzyme activities of dermatophytes and yeast isolates on solid media","volume":"40","author":"Muhsin","year":"1997","journal-title":"Mycoses"},{"key":"ref_37","first-page":"88","article-title":"In vitro toxicological evaluation of carvacrol, thymol and their mixture in Caco-2 cells","volume":"68","author":"Puerto","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_38","first-page":"3136","article-title":"Carvacrol: A natural compound with diverse pharmacological activities","volume":"10","author":"Imran","year":"2022","journal-title":"Food Sci. Nutr."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/12\/7\/462\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T04:16:33Z","timestamp":1782360993000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/12\/7\/462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jof12070462"],"URL":"https:\/\/doi.org\/10.3390\/jof12070462","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]}}}