{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:17:17Z","timestamp":1771611437806,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brazilian agencies Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["310670\/2021-7"],"award-info":[{"award-number":["310670\/2021-7"]}]},{"name":"Brazilian agencies Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["0012017"],"award-info":[{"award-number":["0012017"]}]},{"name":"Brazilian agencies Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["E-26\/201.136\/2021"],"award-info":[{"award-number":["E-26\/201.136\/2021"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["310670\/2021-7"],"award-info":[{"award-number":["310670\/2021-7"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["0012017"],"award-info":[{"award-number":["0012017"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["E-26\/201.136\/2021"],"award-info":[{"award-number":["E-26\/201.136\/2021"]}]},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["310670\/2021-7"],"award-info":[{"award-number":["310670\/2021-7"]}]},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["0012017"],"award-info":[{"award-number":["0012017"]}]},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)","award":["E-26\/201.136\/2021"],"award-info":[{"award-number":["E-26\/201.136\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Candida albicans is an opportunistic fungal pathogen that can cause superficial and life-threatening infections, particularly in immunocompromised individuals. Its ability to adhere to host cells is critical for colonization and infection. In this context, investigating ectophosphatases is particularly relevant, as these enzymes have been associated with fungal adhesion to host cells. This study aimed to investigate the nature of copper-induced stimulation of ectophosphatase activity in C. albicans. Ectophosphatase activity was measured using p-nitrophenyl phosphate as substrate. Micromolar concentrations of CuCl2 markedly stimulated ectophosphatase activity, and its response to reducing agents and metal chelators suggested that this modulation does not involve redox reactions. The significant differences between the biochemical properties of basal (Cu2+-independent) and Cu2+-dependent ectophosphatase activities suggest the presence of at least two distinct ectophosphatases in C. albicans. Cu2+-independent ectophosphatase activity presented an acidic profile and was insensitive to Mg2+, whereas Cu2+-dependent ectophosphatase activity exhibited an alkaline profile and was also stimulated by Mg2+. Both activities were negatively modulated by classical phosphatase inhibitors, but Cu2+-dependent ectophosphatase had lower sensitivity compared to the basal activity. These findings highlight the role of copper as a modulator of C. albicans ectophosphatase activity and suggest potential implications for fungal adaptation during infection.<\/jats:p>","DOI":"10.3390\/pathogens14070667","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T04:18:11Z","timestamp":1751948291000},"page":"667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Copper-Induced Stimulation of Ectophosphatase Activity of Candida albicans"],"prefix":"10.3390","volume":"14","author":[{"given":"Anita Leocadio","family":"Freitas-Mesquita","sequence":"first","affiliation":[{"name":"Leopoldo de Meis Institute of Medical Biochemistry, Center of Health Science, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil"},{"name":"National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro 21941-590, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiano Ferreira","family":"Esteves","sequence":"additional","affiliation":[{"name":"Leopoldo de Meis Institute of Medical Biochemistry, Center of Health Science, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil"},{"name":"National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro 21941-590, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Roberto","family":"Meyer-Fernandes","sequence":"additional","affiliation":[{"name":"Leopoldo de Meis Institute of Medical Biochemistry, Center of Health Science, Federal University of Rio de Janeiro, Rio de Janeiro 21941-590, RJ, Brazil"},{"name":"National Institute of Science and Technology in Structural Biology and Bioimaging, Rio de Janeiro 21941-590, RJ, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kriegl, L., Egger, M., Boyer, J., Hoenigl, M., and Krause, R. (2024). New treatment options for critically important WHO fungal priority pathogens. Clin. Microbiol. Infect., in press.","DOI":"10.1016\/j.cmi.2024.03.006"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"E5336","DOI":"10.1073\/pnas.1513447112","article-title":"Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismutase","volume":"112","author":"Li","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/S1473-3099(10)70218-8","article-title":"Emerging opportunistic yeast infections","volume":"11","author":"Miceli","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4161\/viru.22913","article-title":"Candida albicans pathogenicity mechanisms","volume":"4","author":"Mayer","year":"2013","journal-title":"Virulence"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Keyvanfar, A., Najafiarab, H., Talebian, N., Falah Tafti, M., Adeli, G., Ghasemi, Z., and Tehrani, S. (2024). Drug-resistant oral candidiasis in patients with HIV infection: A systematic review and meta-analysis. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09442-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/j.1601-0825.2009.01644.x","article-title":"Ectophosphatase activity in Candida albicans influences fungal adhesion: Study between HIV-positive and HIV-negative isolates","volume":"16","author":"Portela","year":"2010","journal-title":"Oral Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Talapko, J., Juzba\u0161i\u0107, M., Matijevi\u0107, T., Pustijanac, E., Beki\u0107, S., Kotris, I., and \u0160krlec, I. (2021). Candida albicans\u2014The virulence factors and clinical manifestations of infection. J. Fungi, 7.","DOI":"10.3390\/jof7020079"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1111\/j.1567-1364.2006.00105.x","article-title":"An ectophosphatase activity in Cryptococcus neoformans","volume":"6","author":"Esteves","year":"2006","journal-title":"FEMS Yeast Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00284-012-0296-z","article-title":"Inhibition of ectophosphatase activity in conidia reduces adhesion and virulence of Metarhizium anisopliae on the host insect Dysdercus peruvianus","volume":"66","author":"Santi","year":"2013","journal-title":"Curr. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/j.1567-1364.2007.00223.x","article-title":"An ectophosphatase activity in Candida parapsilosis influences the interaction of fungi with epithelial cells","volume":"7","author":"Pinheiro","year":"2007","journal-title":"FEMS Yeast Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"570","DOI":"10.3109\/13693786.2011.653835","article-title":"Surface phosphatase in Rhinocladiella aquaspersa: Biochemical properties and its involvement with adhesion","volume":"50","author":"Kneipp","year":"2012","journal-title":"Med. Mycol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1099\/mic.0.27405-0","article-title":"Ectophosphatase activity in conidial forms of Fonsecaea pedrosoi is modulated by exogenous phosphate and influences fungal adhesion to mammalian cells","volume":"150","author":"Kneipp","year":"2004","journal-title":"Microbiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.3390\/ijms15022289","article-title":"Biochemical properties and possible roles of ectophosphatase activities in fungi","volume":"15","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Douglas, L.M., and Konopka, J.B. (2019). Plasma membrane architecture protects Candida albicans from killing by copper. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1007911"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"mfad040","DOI":"10.1093\/mtomcs\/mfad040","article-title":"Revisiting the pro-oxidant activity of copper: Interplay of ascorbate, cysteine, and glutathione","volume":"15","author":"Falcone","year":"2023","journal-title":"Metallomics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1073\/pnas.97.7.3520","article-title":"The high copper tolerance of Candida albicans is mediated by a P-type ATPase","volume":"97","author":"Weissman","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/genetics\/134.3.717","article-title":"Isogenic strain construction and gene mapping in Candida albicans","volume":"134","author":"Fonzi","year":"1993","journal-title":"Genetics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1515\/znc-1997-5-613","article-title":"Trypanosoma brucei: Ecto-phosphatase activity on the surface of intact procyclic forms","volume":"52","author":"Fernandes","year":"1997","journal-title":"Z. Naturforsch. C"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0076-6879(79)58132-4","article-title":"Measurement of growth and viability of cells in culture","volume":"58","author":"Patterson","year":"1979","journal-title":"Methods Enzymol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.vetpar.2003.09.012","article-title":"A metallo phosphatase activity present on the surface of Trypanosoma brucei procyclic forms","volume":"118","author":"Fernandes","year":"2003","journal-title":"Vet. Parasitol."},{"key":"ref_21","first-page":"126010","article-title":"Euglena gracilis: Biochemical properties of a membrane bound ecto-phosphatase activity modulated by fluoroaluminate complexes and different trophic conditions","volume":"91","author":"Majerowicz","year":"2023","journal-title":"Eur. J. Protistol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1515\/znc-2007-1-213","article-title":"Effect of copper on acid phosphatase activity in yeast Yarrowia lipolytica","volume":"62","author":"Ito","year":"2007","journal-title":"Z. Naturforsch. C"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s10534-009-9270-z","article-title":"Effect of copper on the activation of the acid phosphatase from the green algae Pseudokirchneriella subcapitata","volume":"23","author":"Jonsson","year":"2010","journal-title":"Biometals"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0378-4274(82)90156-4","article-title":"Effect of copper on tissue acid and alkaline phosphatases in the green snakehead, Ophiocephalus punctatus (Bloch)","volume":"11","author":"Srivastava","year":"1982","journal-title":"Toxicol. Lett."},{"key":"ref_25","first-page":"976","article-title":"Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS","volume":"4","author":"Graham","year":"1991","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s12011-007-8067-6","article-title":"Serum zinc, copper, selenium, calcium, and magnesium levels in pregnant and non-pregnant women in Gondar, Northwest Ethiopia","volume":"122","author":"Kassu","year":"2008","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0048-9697(98)00158-2","article-title":"Serum copper concentration in HIV-infection patients and relationships with other biochemical indices","volume":"217","author":"Moreno","year":"1998","journal-title":"Sci. Total Environ."},{"key":"ref_28","first-page":"105","article-title":"CD4+ T-Cell Count, Serum Zinc, Copper and Selenium Levels in HIV Sero-Positive Subjects on ART and ART Na\u00efve Subjects in Port Harcourt, Nigeria","volume":"10","author":"Onwuli","year":"2022","journal-title":"J. Biosci. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"8040","DOI":"10.3390\/ijms16048040","article-title":"Heavy metal complexation of thiol-containing peptides from soy glycinin hydrolysates","volume":"16","author":"Ding","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0162-0134(00)00212-9","article-title":"Coordination of heavy metals by dithiothreitol, a commonly used thiol group protectant","volume":"84","author":"Lesniak","year":"2001","journal-title":"J. Inorg. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18048","DOI":"10.1021\/acs.inorgchem.1c02669","article-title":"Intermediate Cu(II)-thiolate species in the reduction of Cu(II)GHK by glutathione: A handy chelate for biological Cu(II) reduction","volume":"60","author":"Ufnalska","year":"2021","journal-title":"Inorg. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Shen, J., Griffiths, P.T., Campbell, S.J., Utinger, B., Kalberer, M., and Paulson, S.E. (2021). Ascorbate oxidation by iron, copper and reactive oxygen species: Review, model development, and derivation of key rate constants. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-86477-8"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.exppara.2012.03.001","article-title":"Leishmania amazonensis: Inhibition of 3\u2019-nucleotidase activity by Cu2\u207a ions","volume":"131","year":"2012","journal-title":"Exp. Parasitol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jinorgbio.2011.11.024","article-title":"Coordination chemistry of copper proteins: How nature handles a toxic cargo for essential function","volume":"107","author":"Rubino","year":"2012","journal-title":"J. Inorg. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1110\/ps.35201","article-title":"Differentiation of the slow-binding mechanism for magnesium ion activation and zinc ion inhibition of human placental alkaline phosphatase","volume":"10","author":"Hung","year":"2001","journal-title":"Protein Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"eado5504","DOI":"10.1126\/sciadv.ado5504","article-title":"Magnesium-induced structural reorganization in the active site of adenylate kinase","volume":"10","author":"Nam","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Mackie, J., Szabo, E.K., Urgast, D.S., Ballou, E.R., Childers, D.S., MacCallum, D.M., Feldmann, J., and Brown, A.J.P. (2016). Host-imposed copper poisoning impacts fungal micronutrient acquisition during systemic Candida albicans infections. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158683"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Li, C., Li, Y., and Ding, C. (2019). The role of copper homeostasis at the host-pathogen axis: From bacteria to fungi. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010175"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mib.2021.04.005","article-title":"Local antifungal immunity in the kidney in disseminated candidiasis","volume":"62","author":"Jawale","year":"2021","journal-title":"Curr. Opin. Microbiol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/7\/667\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:06:17Z","timestamp":1760033177000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/7\/667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["pathogens14070667"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14070667","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]}}}