{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:53:36Z","timestamp":1792004016225,"version":"4.4.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Background: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. Objective: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe)2 and nikkomycin Z (nikZ), alone and in association with currently available antifungals (azoles, echinocandins, and polyenes) against Candida auris. Methods: Clinical isolates of C. auris were tested in vitro. (PhSe)2 and nikZ activities were tested alone and in combination with amphotericin B, fluconazole, or the echinocandins, micafungin and caspofungin. Results: (PhSe)2 alone was unable to inhibit C. auris, and antagonism or indifferent effects were observed in the combination of this compound with the antifungals tested. NikZ appeared not active alone either, but frequently acted cooperatively with conventional antifungals. Conclusion: Our data show that (PhSe)2 appears to not have a good potential to be a candidate in the development of new drugs to treat C. auris, but that nikZ is worthy of further study.<\/jats:p>","DOI":"10.3390\/jof8080771","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T21:20:59Z","timestamp":1658784059000},"page":"771","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Initial Results of the International Efforts in Screening New Agents against Candida auris"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7121-3861","authenticated-orcid":false,"given":"Vanice Rodrigues","family":"Poester","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Medicina (FAMED), Universidade Federal do Rio Grande (FURG), Rio Grande 96201-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3538-5006","authenticated-orcid":false,"given":"L\u00edvia Silveira","family":"Munhoz","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Medicina (FAMED), Universidade Federal do Rio Grande (FURG), Rio Grande 96201-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica Louise","family":"Benelli","sequence":"additional","affiliation":[{"name":"Hospital Universit\u00e1rio Dr. Miguel Riet Corr\u00eaa Jr.-HU-FURG\/Empresa Brasileira de Servi\u00e7os Hospitalares\u2014EBSERH, Rio Grande 96201-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6655-8715","authenticated-orcid":false,"given":"Aryse Martins","family":"Melo","sequence":"additional","affiliation":[{"name":"National Institute of Health, Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5206-2647","authenticated-orcid":false,"given":"Abdullah M. S.","family":"Al-Hatmi","sequence":"additional","affiliation":[{"name":"Natural & Medical Science Research Center, University of Nizwa, Nizwa 616, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8202-0483","authenticated-orcid":false,"given":"David J.","family":"Larwood","sequence":"additional","affiliation":[{"name":"California Institute for Medical Research, San Jose, CA 95128, USA"},{"name":"Valley Fever Solutions, Tucson, AZ 85719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marife","family":"Martinez","sequence":"additional","affiliation":[{"name":"California Institute for Medical Research, San Jose, CA 95128, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stevens","sequence":"additional","affiliation":[{"name":"California Institute for Medical Research, San Jose, CA 95128, USA"},{"name":"Division of Infectious Diseases and Geographic Medicine, Stanford University Medical School, Stanford, CA 94305, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-0080","authenticated-orcid":false,"given":"Melissa Orzechowski","family":"Xavier","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Medicina (FAMED), Universidade Federal do Rio Grande (FURG), Rio Grande 96201-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e01588-17","DOI":"10.1128\/JCM.01588-17","article-title":"Candida auris: An Emerging Fungal Pathogen","volume":"56","author":"Spivak","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Du, H., Bing, J., Hu, T., Ennis, C.L., Nobile, C.J., and Huang, G. (2020). Candida auris: Epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008921"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1093\/mmy\/myaa115","article-title":"Ebselen and diphenyl diselenide against fungal pathogens: A systematic review","volume":"59","author":"Benelli","year":"2021","journal-title":"Med. Mycol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e01084-18","DOI":"10.1128\/AAC.01084-18","article-title":"Screening a Repurposing Library for Inhibitors of Multidrug-Resistant Candida auris Identifies Ebselen as a Repositionable Candidate for Antifungal Drug Development","volume":"62","author":"Wall","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fcimb.2019.00083","article-title":"Identification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen Candida auris","volume":"9","author":"Monteiro","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.3389\/fmicb.2020.01673","article-title":"Silver Nanoantibiotics Display Strong Antifungal Activity against the Emergent Multidrug-Resistant Yeast Candida auris Under Both Planktonic and Biofilm Growing Conditions","volume":"11","author":"Lopez","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Billamboz, M., Fatima, Z., Hameed, S., and Jawhara, S. (2021). Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris. Microorganisms, 9.","DOI":"10.3390\/microorganisms9030634"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e01305-20","DOI":"10.1128\/AAC.01305-20","article-title":"Identification of Antifungal Compounds against Multidrug-Resistant Candida auris Utilizing a High-Throughput Drug-Repurposing Screen","volume":"65","author":"Cheng","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"myac008","DOI":"10.1093\/mmy\/myac008","article-title":"Emerging and future strategies in the management of recalcitrant Candida auris","volume":"60","author":"Bandara","year":"2022","journal-title":"Med. Mycol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1742-7843.2007.00073.x","article-title":"Low Toxicity of Diphenyl Diselenide in Rabbits: A Long-Term Study","volume":"101","author":"Portella","year":"2007","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cbi.2006.04.005","article-title":"Changes in biochemical parameters in rabbits blood after oral exposure to diphenyl diselenide for long periods","volume":"162","author":"Portella","year":"2006","journal-title":"Chem. Interact."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1016\/j.lfs.2005.01.029","article-title":"Pro-oxidant action of diphenyl diselenide in the yeast Saccharomyces cerevisiae exposed to ROS-generating conditions","volume":"77","author":"Rosa","year":"2005","journal-title":"Life Sci."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","unstructured":"Larwood, D.J. (2020). Nikkomycin Z\u2014Ready to Meet the Promise?. J. Fungi, 6.","DOI":"10.3390\/jof6040261"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/infdis\/157.1.212","article-title":"Use of the Chitin-Synthesis Inhibitor Nikkomycin to Treat Disseminated Candidiasis in Mice","volume":"157","author":"Becker","year":"1988","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1128\/AAC.34.4.587","article-title":"Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis","volume":"34","author":"Hector","year":"1990","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1099\/00221287-137-9-2155","article-title":"Synergistic action of nikkomycin X\/Z with azole antifungals on Candida albicans","volume":"137","author":"Milewski","year":"1991","journal-title":"J. Gen. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1128\/AAC.43.6.1401","article-title":"In Vitro Antifungal Activity of Nikkomycin Z in Combination with Fluconazole or Itraconazole","volume":"43","author":"Li","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00619-17","DOI":"10.1128\/AAC.00619-17","article-title":"Effects of Echinocandins in Combination with Nikkomycin Z against Invasive Candida albicans Bloodstream Isolates and the fks Mutants","volume":"61","author":"Cheung","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/lam.13204","article-title":"Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms","volume":"69","author":"Nagy","year":"2019","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1128\/AAC.36.6.1284","article-title":"Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo","volume":"36","author":"Hector","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1093\/jac\/dkab052","article-title":"Antifungal activity of nikkomycin Z against Candida auris","volume":"76","author":"Bentz","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","unstructured":"Fromtling, R.A., and Rippon, J.W. (1993). An overview of nikkomycins: History, biochemistry, and applications. Cutaneous Antifungal Agents, Marcel-Dekker, Inc."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mohsin, J., Weerakoon, S., Ahmed, S., Puts, Y., Al Balushi, Z., Meis, J.F., and Al-Hatmi, A.M.S. (2020). A Cluster of Candida auris Blood Stream Infections in a Tertiary Care Hospital in Oman from 2016 to 2019. Antibiotics, 9.","DOI":"10.3390\/antibiotics9100638"},{"key":"ref_25","unstructured":"Paulmier, C. (1986). Selenium reagents and intermediates in organic synthesis. Selenoorganic Functional Groups, Pergamon Press. [1st ed.]."},{"key":"ref_26","unstructured":"Alexander, B. (2017). Reference method for broth dilution antifungal susceptibility testing of yeasts. CLSI Guideline M27, Clinical and Laboratory Standards Institute. [4th ed.]."},{"key":"ref_27","unstructured":"Lorian, V. (1991). Antimicrobial combinations. Antibiotics in Laboratory Medicine, Williams & Wilkins Co.. [3rd ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1128\/AAC.44.6.1624-1629.2000","article-title":"Comparison of Nikkomycin Z with Amphotericin B and Itraconazole for Treatment of Histoplasmosis in a Murine Model","volume":"44","author":"Goldberg","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.2460\/ajvr.2005.66.1090","article-title":"Comparison of susceptibility of fungal isolates to lufenuron and nikkomycin Z alone or in combination with itraconazole","volume":"66","author":"Hector","year":"2005","journal-title":"Am. J. Veter-Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/mmy\/myy044","article-title":"Antifungal activity of diphenyl diselenide alone and in combination with itraconazole against Sporothrix brasiliensis","volume":"57","author":"Poester","year":"2019","journal-title":"Med. Mycol."},{"key":"ref_31","unstructured":"Centers for Disease Control and Prevention (2022, May 18). Antifungal Susceptibility Testing and Interpretation 2020, Available online: https:\/\/www.cdc.gov\/fungal\/candida-auris\/c-auris-antifungal.html."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1093\/mmy\/myaa072","article-title":"Diphenyl diselenide and its interaction with antifungals against Aspergillus spp.","volume":"59","author":"Melo","year":"2020","journal-title":"Med. Mycol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/mmy\/myaa054","article-title":"Potential use of Nikkomycin Z as an anti- Sporothrix spp. drug","volume":"59","author":"Poester","year":"2021","journal-title":"Med. Mycol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1128\/AAC.38.12.2843","article-title":"Effects of antifungal agent combinations administered simultaneously and sequentially against Aspergillus fumigatus","volume":"38","author":"Maesaki","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1128\/AAC.48.9.3407-3411.2004","article-title":"Paradoxical Effect of Caspofungin: Reduced Activity against Candida albicans at High Drug Concentrations","volume":"48","author":"Stevens","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1016\/j.bbagen.2016.09.029","article-title":"Ebselen exerts antifungal activity by regulating glutathione (GSH) and reactive oxygen species (ROS) production in fungal cells","volume":"1861","author":"Thangamani","year":"2016","journal-title":"Biochim. et Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s10787-020-00690-x","article-title":"Selenium and selenoproteins: It\u2019s role in regulation of inflammation","volume":"28","author":"Hariharan","year":"2020","journal-title":"Inflammopharmacology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e21892","DOI":"10.1002\/jbt.21892","article-title":"In vitro assessment of the growth and plasma membrane H+-ATPase inhibitory activity of ebselen and structurally related selenium- and sulfur-containing compounds in Candida albicans","volume":"31","author":"Orie","year":"2017","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1248\/cpb.56.1423","article-title":"New Organoselenium Compounds Active against Pathogenic Bacteria, Fungi and Viruses","volume":"56","author":"Piasecki","year":"2008","journal-title":"Chem. Pharm. Bull."},{"key":"ref_40","unstructured":"Fromtling, R.A., and Rippon, J.W. (1993). Interactions between chitin and beta-glucan synthesis inhibitors. An new approach to antifungal development for cutaneous infections. Cutaneous Antifungal Agents, Marcel-Dekker, Inc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1128\/AAC.44.9.2547-2548.2000","article-title":"Drug Interaction Studies of a Glucan Synthase Inhibitor (LY 303366) and a Chitin Synthase Inhibitor (Nikkomycin Z) for Inhibition and Killing of Fungal Pathogens","volume":"44","author":"Stevens","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/yea.837","article-title":"Inhibitory effect of nikkomycin Z on chitin synthases in Candida albicans","volume":"19","author":"Kim","year":"2002","journal-title":"Yeast"}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/8\/771\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:56:00Z","timestamp":1760140560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/8\/8\/771"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,25]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["jof8080771"],"URL":"https:\/\/doi.org\/10.3390\/jof8080771","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,25]]}}}