{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:33Z","timestamp":1760145633797,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brazil (CAPES)","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Although Candida albicans is the most frequently identified Candida species in clinical settings, a significant number of infections related to the non-albicans Candida (NAC) species, Candida krusei, has been reported. Both species are able to produce biofilms and have been an important resistance-related factor to antimicrobial resistance. In addition, the microbial relationship is common in the human body, contributing to the formation of polymicrobial biofilms. Considering the great number of reports showing the increase in cases of resistance to the available antifungal drugs, the development of new and effective antifungal agents is critical. The inhibitory effect of Organoselenium Compounds (OCs) on the development of Candida albicans and Candida krusei was recently demonstrated, supporting the potential of these compounds as efficient antifungal drugs. In addition, OCs were able to reduce the viability and the development of biofilms, a very important step in colonization and infection caused by fungi. Thus, the objective of this study was to investigate the effect of the Organoselenium Compounds (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2 on the development of dual-species biofilms of Candida albicans and Candida krusei produced using either RPMI-1640 or Sabouraud Dextrose Broth (SDB) media. The development of dual-species biofilms was evaluated by the determination of both metabolic activity, using a metabolic assay based on the reduction of XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt) assay and identification of either Candida albicans and Candida krusei on CHROMagar Candida medium. Biofilm formation using RPMI-1640 was inhibited in 90, 55, and 20% by 30 \u00b5M (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively. However, biofilms produced using SDB presented an inhibition of 62, 30 and 15% in the presence of 30 \u00b5M (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively. The metabolic activity of 24 h biofilms was inhibited by 35, 30 and 20% by 30 \u00b5M (p-MeOPhSe)2, (PhSe)2, and (p-Cl-PhSe)2, respectively, with RPMI-1640; however, 24 h biofilms formed using SDB were not modified by the OCs. In addition, a great reduction in the number of CFUs of Candida albicans (93%) in biofilms produced using RPMI-1640 in the presence of 30 \u00b5M (p-MeOPhSe)2 was observed. However, biofilms formed using SDB and treated with 30 \u00b5M (p-MeOPhSe)2 presented a reduction of 97 and 69% in the number of CFUs of Candida albicans and Candida krusei, respectively. These results demonstrated that Organoselenium Compounds, mainly (p-MeOPhSe)2, are able to decrease the metabolic activity of dual-species biofilms by reducing both Candida albicans and Candida krusei cell number during biofilm formation using either RPMI-1640 or SDB. Taken together, these results demonstrated the potential of the OCs to inhibit the development of dual-species biofilms of Candida albicans and Candida krusei.<\/jats:p>","DOI":"10.3390\/ph17081078","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T06:23:20Z","timestamp":1723789400000},"page":"1078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Development and Metabolism of Dual-Species Biofilms of Candida albicans and Candida krusei (Pichia kudriavzevii) by Organoselenium Compounds"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7497-6158","authenticated-orcid":false,"given":"Gabriela de Souza","family":"Calvi","sequence":"first","affiliation":[{"name":"Instituto de Pesquisa & Desenvolvimento\u2014IP&D, Universidade do Vale do Para\u00edba\u2014UNIVAP, Av. Shishima Hifumi, 2911, S\u00e3o Jos\u00e9 dos Campos 12244-390, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5365-4953","authenticated-orcid":false,"given":"Giulia Nicolle J\u00e1come","family":"Cartaxo","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa & Desenvolvimento\u2014IP&D, Universidade do Vale do Para\u00edba\u2014UNIVAP, Av. Shishima Hifumi, 2911, S\u00e3o Jos\u00e9 dos Campos 12244-390, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuxin Lin","family":"Carretoni","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa & Desenvolvimento\u2014IP&D, Universidade do Vale do Para\u00edba\u2014UNIVAP, Av. Shishima Hifumi, 2911, S\u00e3o Jos\u00e9 dos Campos 12244-390, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 Luiz Missio","family":"da Silva","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa & Desenvolvimento\u2014IP&D, Universidade do Vale do Para\u00edba\u2014UNIVAP, Av. Shishima Hifumi, 2911, S\u00e3o Jos\u00e9 dos Campos 12244-390, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denilson Nogueira","family":"de Moraes","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa & Desenvolvimento\u2014IP&D, Universidade do Vale do Para\u00edba\u2014UNIVAP, Av. Shishima Hifumi, 2911, S\u00e3o Jos\u00e9 dos Campos 12244-390, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2902-0983","authenticated-orcid":false,"given":"Jos\u00e9 Geraldo da Cruz","family":"Pradella","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa & Desenvolvimento\u2014IP&D, Universidade do Vale do Para\u00edba\u2014UNIVAP, Av. Shishima Hifumi, 2911, S\u00e3o Jos\u00e9 dos Campos 12244-390, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0141-7241","authenticated-orcid":false,"given":"Maricilia Silva","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa & Desenvolvimento\u2014IP&D, Universidade do Vale do Para\u00edba\u2014UNIVAP, Av. 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Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.micinf.2016.01.002","article-title":"Candida albicans biofilms: Development, regulation, and molecular mechanisms","volume":"18","author":"Gulati","year":"2016","journal-title":"Microbes Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1080\/21505594.2020.1748930","article-title":"The regulation of hyphae growth in Candida albicans","volume":"11","author":"Chen","year":"2020","journal-title":"Virulence"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/1469-0691.12539","article-title":"Global trends in the distribution of Candida species causing candidemia","volume":"20","author":"Guinea","year":"2014","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ijantimicag.2013.09.005","article-title":"Nosocomial bloodstream infections due to Candida sin the USA: Species distribution, clinical features and antifungal susceptibilities","volume":"43","author":"Wisplinghoff","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Whaley, S.G., Berkow, E.L., Rybak, J.M., Nishimoto, A.T., Barker, K.S., and Rogers, P.D. (2017). Azole antifungal resistance in Candida albicans and emerging non-albicans Candida Species. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.02173"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/mmy\/myaa031","article-title":"Update on Candida krusei, a potential multidrug-resistant pathogen","volume":"59","author":"Jamiu","year":"2021","journal-title":"Med. Mycol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-micro-091014-104330","article-title":"Candida albicans Biofilms and Human Disease","volume":"69","author":"Nobile","year":"2015","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kaur, J., and Nobile, C.J. (2023). Antifungal drug-resistance mechanisms in Candida biofilms. Curr. Opin. Microbiol., 71.","DOI":"10.1016\/j.mib.2022.102237"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Malinovsk\u00e1, Z., \u010conkov\u00e1, E., and V\u00e1czi, P. (2023). Biofilm Formation in Medically Important Candida Species. J. Fungi, 9.","DOI":"10.3390\/jof9100955"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/1040841X.2020.1843400","article-title":"Candida albicans biofilms and polymicrobial interactions","volume":"47","author":"Ponde","year":"2021","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.mib.2011.06.001","article-title":"Mucosal biofilms of Candida albicans","volume":"14","author":"Ganguly","year":"2011","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"ftw018","DOI":"10.1093\/femspd\/ftw018","article-title":"Pathogenesis of Candida albicans biofilm","volume":"74","author":"Tsui","year":"2016","journal-title":"Pathog. Dis."},{"key":"ref_16","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_17","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.idc.2021.08.002","article-title":"Nosocomial Fungal Infections: Epidemiology, Infection Control, and Prevention","volume":"35","author":"Suleyman","year":"2021","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Bongomin, F., Gago, S., Oladele, R.O., and Denning, D.W. (2017). Global and multi-national prevalence of fungal diseases\u2014Estimate precision. J. Fungi, 3.","DOI":"10.3390\/jof3040057"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s00134-020-05950-6","article-title":"Bloodstream infections in critically ill patients: An expert statement","volume":"46","author":"Timsit","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41579-023-00861-x","article-title":"The WHO fungal priority pathogens list as a game-changer","volume":"21","author":"Fisher","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Garvey, M., and Rowan, N.J. (2023). Pathogenic Drug Resistant Fungi: A Review of Mitigation Strategies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021584"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1021\/om9603878","article-title":"Organic-Organometallic Crystal Synthesis. 1. HostingParamagnetic [(\u03b76-Arene)2 Cr] + (Arene) Benzene, Toluene) in Organic Anion Frameworks via OsH\u201a\u201a\u201aO andCsH\u201a\u201a\u201aO Hydrogen Bonds","volume":"16","author":"Braga","year":"1997","journal-title":"Organometallics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.mrgentox.2009.01.003","article-title":"3\u20323-ditrifluoromethyldiphenyl diselenide: A new organoselenium compound with interesting antigenotoxic and antimutagenic activities","volume":"17","author":"Machado","year":"2009","journal-title":"Mutat. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Giurg, M., Golab, A., Suchodolski, J., Kaleta, R., Krasowska, A., Piasecki, E., and Pi\u0119tka-Ottlik, M. (2017). Reaction of bis[(2-chlorocarbonyl)phenyl] Diselenide with Phenols, Aminophenols, and Other Amines towards Diphenyl Diselenides with Antimicrobial and Antiviral Properties. Molecules, 12.","DOI":"10.3390\/molecules22060974"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6255","DOI":"10.1021\/cr0406559","article-title":"Organoselenium and Organotellurium Compounds: Toxicology and Pharmacology","volume":"104","author":"Nogueira","year":"2004","journal-title":"Chem. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1439-0507.2010.01888.x","article-title":"Candida albicans growth and germ tube formation can be inhibited by simple diphenyl diselenides [(PhSe) 2, (MeOPhSe) 2, (p-Cl-PhSe) 2, (F 3CPhSe) 2] and diphenyl ditelluride","volume":"54","author":"Rosseti","year":"2011","journal-title":"Mycoses"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"589","DOI":"10.2174\/1570193X16666181227111038","article-title":"Synthetic Approaches to Organoselenium Derivatives with Antimicrobial and Anti-Biofilm Activity","volume":"16","author":"Messina","year":"2019","journal-title":"Mini-Rev. Org.-Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.00924-20","article-title":"Screening Repurposing Libraries for Identification of Drugs with Novel Antifungal Activity","volume":"64","author":"Wall","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jtemb.2014.08.001","article-title":"Diphenyl diselenide (PhSe)2 inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability","volume":"29","author":"Rosseti","year":"2015","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_30","first-page":"3964","article-title":"The Organochalcogen Compound (MeOPhSe)2 Inhibits Both Formation and the Viability of the Biofilm Produced by Candida albicans, at Different Stages of Development","volume":"24","author":"Braga","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1080\/08927014.2021.1897110","article-title":"(PhSe)2 and (pCl-PhSe)2 organochalcogen compounds inhibit Candida albicans adhesion to human endocervical (HeLa) cells and show anti-biofilm activities","volume":"37","author":"Braga","year":"2021","journal-title":"Biofouling"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"de Siqueira, V.M., da Silva, B.G.M., Passos, J.C.d.S., Pinto, A.P., da Rocha, J.B.T., Alberto-Silva, C., and Costa, M.S. (2022). (MeOPhSe)2, a synthetic organic selenium compound, inhibits virulence factors of Candida krusei: Adherence to cervical epithelial cells and biofilm formation. J. Trace Elem. Med. Biol., 73.","DOI":"10.1016\/j.jtemb.2022.127019"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1080\/08927014.2022.2084388","article-title":"Diphenyl diselenide suppresses key virulence factors of Candida krusei, a neglected fungal pathogen","volume":"38","author":"Pinto","year":"2022","journal-title":"Biofouling"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1021\/acs.chemrev.2c00431","article-title":"Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies","volume":"123","author":"Aggarwal","year":"2023","journal-title":"Chem. Rev."},{"key":"ref_35","first-page":"10","article-title":"\u201cIt takes a village\u201d: Mechanisms underlying antimicrobial recalcitrance of polymicrobial biofilms","volume":"202","author":"Orazi","year":"2020","journal-title":"J. Bacteriol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tits, J., Cammue, B.P.A., and Thevissen, K. (2020). Combination therapy to treat fungal biofilm-based infections. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228873"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101215","DOI":"10.1016\/j.mam.2023.101215","article-title":"The changing epidemiology of fungal infections","volume":"94","author":"Steixner","year":"2023","journal-title":"Mol. Asp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1086\/591033","article-title":"Secular Trends in Candidemia-Related Hospitalization in the United States, 2000\u20132005","volume":"29","author":"Zilberberg","year":"2008","journal-title":"Infect. Control. Hosp. Epidemiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/j.cmi.2019.04.024","article-title":"Morbidity and mortality of candidaemia in Europe: An epidemiologic meta-analysis","volume":"25","author":"Koehler","year":"2019","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/myc.13137","article-title":"Oropharyngeal candidiasis in hospitalised COVID-19 patients from Iran: Species identification and antifungal susceptibility pattern","volume":"63","author":"Salehi","year":"2020","journal-title":"Mycoses"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"103787","DOI":"10.1016\/j.pdpdt.2023.103787","article-title":"The inhibitory effect of photodynamic therapy on dual-species biofilms of Candida albicans and Candida krusei can be determined by Candida albicans\/Candida krusei ratio","volume":"44","author":"Passos","year":"2023","journal-title":"Photodiagnosis Photodyn Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/08927014.2024.2389848","article-title":"The arrangement of dual-species biofilms of Candida albicans and Issatchenkia orientalis can be modified by the medium: Effect of Voriconazole","volume":"8","author":"Passos","year":"2024","journal-title":"Biofouling"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1590\/S0103-50532010001100013","article-title":"Genetic toxicity of three symmetrical diselenides in yeast","volume":"21","author":"Rosa","year":"2010","journal-title":"J. Braz. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S1074-5521(03)00174-1","article-title":"Metal and redox modulation of cysteine protein function","volume":"10","author":"Giles","year":"2003","journal-title":"Chem. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"\u017diemyt\u0117, M., Rodr\u00edguez-D\u00edaz, J.C., Ventero-Mart\u00edn, M.P., Mira, A., and Ferrer, M.D. (2023). Real-time monitoring of biofilm growth identifies andrographolide as a potent antifungal compound eradicating Candida biofilm. Biofilm, 5.","DOI":"10.1016\/j.bioflm.2023.100134"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s40121-020-00382-7","article-title":"Sixty years of Amphotericin B: An Overview of the Main Antifungal Agent Used to Treat Invasive Fungal Infections","volume":"10","author":"Cavassin","year":"2021","journal-title":"Infect. Dis. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S244","DOI":"10.1093\/cid\/ciz064","article-title":"Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B","volume":"68","author":"Lewis","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_48","unstructured":"Paulmier, C. (1986). Selenium Reagents and Intermediates in Organic Synthesis, Elsevier."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/8\/1078\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:37:38Z","timestamp":1760110658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/8\/1078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,16]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ph17081078"],"URL":"https:\/\/doi.org\/10.3390\/ph17081078","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2024,8,16]]}}}